Drug Structure Function & design

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Questions and Answers

What role do functional groups play in drug molecules?

  • They predict the chemical properties of the drug. (correct)
  • They define the color of the drug.
  • They determine the drug's manufacturing process.
  • They control the drug's packaging requirements.

Which of the following describes the correct sequence of drug administration and action?

  • The drug interacts with a target, then is ingested.
  • The drug is absorbed, then it interacts with the target.
  • The drug is administered, then travels to its site of activity. (correct)
  • The drug is injected, then expelled from the body.

Which property can NOT be predicted by recognizing the functional groups in a drug?

  • Reactivity and stability
  • Acid/base properties
  • Patient's age (correct)
  • Solubility

What is primarily discussed in relation to protein structure in the context of drug interactions?

<p>The forces involved in controlling protein structure. (A)</p> Signup and view all the answers

What is a vital aspect of understanding drug molecules?

<p>Their effect on the body depends on the binding forces with targets. (D)</p> Signup and view all the answers

Which transport mechanism allows drug molecules to move across cell membranes without the use of energy?

<p>Passive diffusion (D)</p> Signup and view all the answers

What is primarily targeted by drugs in the body?

<p>Nucleic acids (C)</p> Signup and view all the answers

Which of the following routes of drug administration bypasses the gastrointestinal tract?

<p>Intramuscular (A), Sublingual (B), Buccal (D)</p> Signup and view all the answers

What type of drug interaction primarily involves a specific area of a protein?

<p>Receptor activation (B)</p> Signup and view all the answers

What are the primary sites for drug metabolism in the body?

<p>Liver and kidneys (C)</p> Signup and view all the answers

Which of the following accurately describes facilitated diffusion?

<p>Does not require energy and uses specific transport proteins (B)</p> Signup and view all the answers

Which drug administration route directly delivers medication into the bloodstream?

<p>Intravenous (A)</p> Signup and view all the answers

What process allows cells to engulf liquid during drug absorption?

<p>Pinocytosis (A)</p> Signup and view all the answers

What defines the primary structure of a protein?

<p>The sequence of amino acids (D)</p> Signup and view all the answers

Which type of bond is not typically involved in tertiary protein structure?

<p>Peptide bonds (C)</p> Signup and view all the answers

Which force of attraction is the weakest among those that stabilize tertiary protein structure?

<p>Van der Waals interactions (D)</p> Signup and view all the answers

How do drugs generally interact with their target proteins?

<p>Using primarily non-covalent, reversible interactions (C)</p> Signup and view all the answers

Which of the following statements about protein structure is incorrect?

<p>Primary structure includes alpha helices and beta sheets. (D)</p> Signup and view all the answers

Which of the following molecules can act as targets for drugs?

<p>Proteins, lipids, nucleic acids, and carbohydrates (A)</p> Signup and view all the answers

What primarily determines the ability of a drug to bond intermolecularly with its target?

<p>The functional group structure of the drug (A)</p> Signup and view all the answers

Which of the following interactions is typically non-reversible?

<p>Covalent bonding (C)</p> Signup and view all the answers

What is the significance of stereochemistry in drug molecules?

<p>Stereochemistry influences how a drug interacts with its target, affecting its efficacy and safety.</p> Signup and view all the answers

Explain how functional groups can predict the solubility of a drug.

<p>Functional groups affect the polarity of a drug molecule, which in turn determines its solubility in water or lipids.</p> Signup and view all the answers

Identify the type of forces that govern the binding between drugs and their target proteins.

<p>The binding forces between drugs and target proteins include hydrogen bonds, ionic interactions, and hydrophobic interactions.</p> Signup and view all the answers

What role does ionization play in drug absorption?

<p>Ionization affects a drug's solubility and permeability, influencing how well it can be absorbed in the gastrointestinal tract.</p> Signup and view all the answers

How can recognizing functional groups in drugs assist in predicting their reactivity?

<p>Recognizing functional groups helps anticipate chemical behavior, such as reactions with biological molecules or degradation pathways.</p> Signup and view all the answers

What are the four basic transport mechanisms for drug absorption?

<p>The four basic transport mechanisms are passive diffusion, facilitated diffusion, active transport, and pinocytosis.</p> Signup and view all the answers

Why are proteins and nucleic acids considered primary drug targets?

<p>Proteins and nucleic acids are primary drug targets because they play crucial roles in cellular functions and interactions.</p> Signup and view all the answers

How does active transport differ from passive diffusion in drug absorption?

<p>Active transport requires energy to move drug molecules against their concentration gradient, while passive diffusion does not require energy.</p> Signup and view all the answers

What is meant by tissue diffusion in the context of drug distribution?

<p>Tissue diffusion refers to the process by which drug molecules spread from the bloodstream into various tissues.</p> Signup and view all the answers

In what way do lipids, carbohydrates, and proteins act as drug targets?

<p>Lipids, carbohydrates, and proteins can act as drug targets because they can interact with drug molecules to elicit biological effects.</p> Signup and view all the answers

Explain the significance of the liver in drug metabolism.

<p>The liver is significant in drug metabolism as it is the primary site where drugs are chemically altered before excretion.</p> Signup and view all the answers

What role does the kidney play in drug excretion?

<p>The kidney plays a critical role in drug excretion by filtering and eliminating waste products from the bloodstream.</p> Signup and view all the answers

Define pinocytosis and its importance in drug absorption.

<p>Pinocytosis is the process by which cells engulf liquid containing drug molecules, allowing for absorption.</p> Signup and view all the answers

What is the main characteristic of a protein's primary structure?

<p>The primary structure of a protein is simply the order of individual amino acids linked together by peptide bonds.</p> Signup and view all the answers

Describe the two types of secondary protein structures.

<p>The two types of secondary structures are alpha helices, which are coiled and held together by hydrogen bonds, and beta-pleated sheets, which are layered and also stabilized by hydrogen bonds.</p> Signup and view all the answers

How does the tertiary structure of a protein relate to its function?

<p>The tertiary structure represents the overall 3D shape of a protein, which is essential for its functionality and interactions with other molecules, including drugs.</p> Signup and view all the answers

Identify and explain the strongest bond involved in tertiary protein structures.

<p>The strongest bond in tertiary structures is the covalent bond, such as disulfide bonds formed between cysteine residues.</p> Signup and view all the answers

What role do ionic bonds play in protein tertiary structure?

<p>Ionic bonds act as strong bonding forces between groups with opposite charges, contributing to the stability of the protein's tertiary structure.</p> Signup and view all the answers

How do van der Waals interactions contribute to protein structure?

<p>Van der Waals interactions are weak forces that occur between hydrophobic molecules, aiding in the proper folding and stability of protein structures.</p> Signup and view all the answers

What are the main types of interactions that facilitate drug-target binding?

<p>The main types of interactions for drug-target binding include ionic interactions, hydrogen bonding, van der Waals interactions, and dipole-dipole interactions.</p> Signup and view all the answers

Explain why covalent bonds in drug-target interactions are often considered irreversible.

<p>Covalent bonds are typically stronger and, once formed, can permanently modify the target protein, categorizing them as irreversible interactions.</p> Signup and view all the answers

What are the two components involved in hydrogen bonding as described in drug interactions?

<p>Hydrogen bond donor and hydrogen bond acceptor (B)</p> Signup and view all the answers

Which of the following are characteristics of van der Waals interactions in drug molecules?

<p>Depend on the polarization of bonds in functional groups (A)</p> Signup and view all the answers

How do hydroxyl groups in alcohols and phenols contribute to drug interactions?

<p>They participate in hydrogen bonding (B)</p> Signup and view all the answers

What is the role of the COO– group in the binding of adrenaline to its target?

<p>It serves as hydrogen bond acceptor (A)</p> Signup and view all the answers

Which property is commonly associated with the functional groups in drugs?

<p>Influences solubility and reactivity (D)</p> Signup and view all the answers

What type of interaction is characterized by the ability of hydrogen to carry a positive charge at physiological pH?

<p>Hydrogen bonding (D)</p> Signup and view all the answers

Why are carboxylic acid side chains important in the context of drug action?

<p>They allow for the formation of ionic bonds with targets (A)</p> Signup and view all the answers

What determines the strength of a hydrogen bond in drug interactions?

<p>The electronegativity of the atoms involved (B)</p> Signup and view all the answers

Which functional group is primarily a hydrogen bond donor in drug interactions?

<p>Hydroxyl group (D)</p> Signup and view all the answers

How do van der Waals interactions influence drug-target binding?

<p>They create a temporary attraction between molecules that can enhance binding strength. (A)</p> Signup and view all the answers

Which modification to a drug molecule could potentially increase its solubility due to the introduction of functional groups?

<p>Introducing a carboxylic acid group (D)</p> Signup and view all the answers

What role do functional groups play in determining a drug's reactivity?

<p>They define the binding affinity with target proteins. (C)</p> Signup and view all the answers

What is a characteristic of carboxylic acids that enhances their role in drug chemistry?

<p>They can act both as hydrogen bond donors and acceptors. (B)</p> Signup and view all the answers

Which type of bond is primarily responsible for the strength of drug-target interactions when involving functional groups?

<p>Hydrogen bonds (D)</p> Signup and view all the answers

What effect do modifications of functional groups on a drug have?

<p>They can change the drug's solubility and absorption properties. (A)</p> Signup and view all the answers

Which property of carboxylic acids contributes to their effectiveness as drug molecules?

<p>Their capacity to ionize and participate in metabolic reactions. (B)</p> Signup and view all the answers

What are the roles of hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs) in drug interactions?

<p>Both HBDs and HBAs can facilitate multiple types of drug interactions. (C)</p> Signup and view all the answers

Which statement accurately describes the ability of ethers in hydrogen bond interactions?

<p>Ethers cannot act as HBDs and are poor HBAs due to steric hindrance. (A)</p> Signup and view all the answers

How do van der Waals interactions contribute to drug-target interactions?

<p>They are most significant in drug molecules with non-polar groups. (C)</p> Signup and view all the answers

What structural modifications can impact the binding ability of drugs?

<p>Converting the OH group to an ether or ester functional group. (C)</p> Signup and view all the answers

What is the role of aromatic rings in the context of drug molecules?

<p>They facilitate van der Waals interactions with target sites. (B)</p> Signup and view all the answers

Which of these factors primarily affects the functionality of carboxylic acids in drug interactions?

<p>Their capacity to establish ionic and hydrogen bonds. (B)</p> Signup and view all the answers

Why might modifying a drug's functional group impact its interaction with the target?

<p>Modification can alter the drug's solubility and binding characteristics. (C)</p> Signup and view all the answers

What type of forces can play a role in drug-target interactions beyond hydrogen bonding?

<p>Covalent, ionic, ion-dipole, hydrogen bonding, and van der Waals forces. (D)</p> Signup and view all the answers

What types of interactions are involved in bonding between adrenaline and its target?

<p>Ionic bonds and hydrogen bonds are involved in bonding between adrenaline and its target.</p> Signup and view all the answers

Explain the significance of hydrogen bonds in drug solubility and boiling point.

<p>Hydrogen bonds contribute to drug solubility and influence boiling points by stabilizing molecular interactions.</p> Signup and view all the answers

How do functional groups like alcohols and phenols facilitate drug interactions?

<p>Alcohols and phenols facilitate drug interactions by forming hydrogen bonds with target molecules.</p> Signup and view all the answers

What is the bond strength range for hydrogen bonds as mentioned in the content?

<p>The bond strength range for hydrogen bonds is 7-40 kJ mol-1.</p> Signup and view all the answers

In the context of drug interactions, what role does anionic groups play in bonding?

<p>Anionic groups form ionic bonds with positively charged regions on target molecules.</p> Signup and view all the answers

What are the two components of hydrogen bonding as it pertains to drug interactions?

<p>The two components are the hydrogen bond donor (HBD) and the hydrogen bond acceptor (HBA).</p> Signup and view all the answers

Why is adrenaline considered to have two phenolic OH groups in its structure?

<p>Adrenaline contains two phenolic OH groups which are crucial for forming hydrogen bonds with its targets.</p> Signup and view all the answers

Describe the effect of electronegative atoms on dipole-dipole interactions in drug binding.

<p>Electronegative atoms create a polarized distribution of electrons, enhancing dipole-dipole interactions.</p> Signup and view all the answers

What is the primary factor that allows drugs to effectively bind with their targets?

<p>The primary factor is the presence of specific interactions such as hydrogen bonds, ionic bonds, and covalent bonds.</p> Signup and view all the answers

Explain the significance of amine groups in drug interactions.

<p>Amine groups are basic and can become ionized at physiological pH, allowing them to participate in ionic interactions with drug targets.</p> Signup and view all the answers

How do covalent bonds compare to other types of bonds in terms of strength in drug-target interactions?

<p>Covalent bonds are the strongest type of bonding force in drug-target interactions, making them relatively stable and often irreversible.</p> Signup and view all the answers

Describe the role of the active site in drug-target interactions.

<p>The active site is where the drug binds to the target, typically located on or near the surface of the protein, much like a lock and key.</p> Signup and view all the answers

What is the distinction between hydrogen bond donors and acceptors?

<p>Hydrogen bond donors possess a hydrogen atom attached to an electronegative atom while acceptors are electronegative atoms that can form a bond with the hydrogen.</p> Signup and view all the answers

How do ionic bonds contribute to drug interaction over distances?

<p>Ionic bonds can attract opposite charges over greater distances than other bonding forces, allowing for persistent interactions.</p> Signup and view all the answers

What kind of structural changes can covalent bonding induce in drug molecules?

<p>Covalent bonding can result in permanent modifications to the drug molecule's structure, affecting its function and pharmacodynamics.</p> Signup and view all the answers

What role do functional groups play in establishing hydrogen bonding in drug molecules?

<p>Functional groups determine the ability of a drug to act as either a hydrogen bond donor or acceptor, influencing binding interactions.</p> Signup and view all the answers

What happens to the binding properties of a drug when its hydroxyl (OH) group is replaced with an ether functional group?

<p>The drug can no longer act as a hydrogen bond donor (HBD) and becomes a poor hydrogen bond acceptor (HBA) due to steric hindrance.</p> Signup and view all the answers

Describe the role of London Dispersion Forces in drug interactions.

<p>London Dispersion Forces facilitate interactions between non-polar groups, such as aromatic rings and aliphatic side chains, enhancing drug-target binding.</p> Signup and view all the answers

In the context of adrenaline's structure, how do multiple interactions impact its binding to target sites?

<p>Adrenaline's structure interacts with various parts of the target, leading to a stronger overall binding due to the contribution of multiple forces.</p> Signup and view all the answers

Why are ethers considered poor hydrogen bond acceptors in drug interactions?

<p>Ethers face steric hindrance that prevents them from effectively accepting hydrogen bonds.</p> Signup and view all the answers

How does the structural presence of an aromatic ring in a drug like adrenaline influence its interactions?

<p>The aromatic ring can form van der Waals interactions with the target, enhancing the stability and specificity of binding.</p> Signup and view all the answers

What types of molecular interactions may contribute to the binding of drugs, as mentioned in the content?

<p>Covalent, ionic, ion-dipole, hydrogen bonding, and van der Waals forces may all play a role in drug-target interactions.</p> Signup and view all the answers

Explain the significance of hydrogen bond donors (HBDs) and acceptors (HBAs) in drug molecular interactions.

<p>HBDs donate hydrogen atoms to form bonds with acceptors, influencing the strength and specificity of drug-target interactions.</p> Signup and view all the answers

What changes occur when a drug's functional groups are modified to examine their roles in binding?

<p>Modifying functional groups like the hydroxyl group can determine if they are essential for binding as HBDs or HBAs by altering their participatory roles.</p> Signup and view all the answers

What typical modification can be made to aromatic groups when testing the Structure-Activity Relationship (SAR) of a drug?

<p>Change them to saturated carbon chains (C)</p> Signup and view all the answers

Which functional group can act as both a hydrogen bond donor and acceptor?

<p>Amines (A)</p> Signup and view all the answers

In prodrug formation, which functional group is primarily utilized to enhance membrane permeability?

<p>Esters (B)</p> Signup and view all the answers

What best describes a pharmacophore in drug design?

<p>The arrangement of functional groups necessary for biological activity (D)</p> Signup and view all the answers

What is a key objective when working out Structure-Activity Relationships (SARs) in drug development?

<p>To identify essential functional groups that enhance drug activity (A)</p> Signup and view all the answers

What is the significance of converting carboxylic acids to esters in drug interactions?

<p>Esters cannot engage in hydrogen bonding. (A)</p> Signup and view all the answers

How do drugs utilize hydrogen bonding in their interactions with targets?

<p>As both hydrogen bond donors and acceptors. (A)</p> Signup and view all the answers

In the context of structure-activity relationships, which factor is critical for a lead compound's optimization?

<p>The steric effects of substituents. (D)</p> Signup and view all the answers

Which type of force is primarily responsible for interactions between alkenes and their binding sites?

<p>Van der Waals forces. (A)</p> Signup and view all the answers

What role do prodrugs play in drug delivery?

<p>They require metabolic activation to become effective. (C)</p> Signup and view all the answers

Which statement is true regarding the importance of hydrogen bonding in drug-target interactions?

<p>Hydrogen bonds can increase specificity in drug interactions. (D)</p> Signup and view all the answers

Which aspect of pharmacophores is primarily influenced by chemical functional groups?

<p>The spatial arrangement and types of interactions. (B)</p> Signup and view all the answers

What impact does the presence of fatty barriers, such as cell membranes, have on drug activity?

<p>Fatty barriers restrict drug permeation and action. (C)</p> Signup and view all the answers

What is the aim of studying Structure-Activity Relationships (SARs) in drug development?

<p>To determine which functional groups are essential for biological activity. (B)</p> Signup and view all the answers

Which statement accurately reflects the role of a lead compound in pharmacology?

<p>It is the starting point for developing more effective drug analogues. (D)</p> Signup and view all the answers

What does the pharmacophore of a drug signify?

<p>The necessary functional groups for binding and activity. (D)</p> Signup and view all the answers

In the context of hydrogen bonding, which types of amines can act as hydrogen bond donors?

<p>Primary and secondary amines. (A)</p> Signup and view all the answers

When modifying a drug structure to test for activity, what does it indicate if the modified structure shows decreased activity?

<p>The changed functional group is important for biological activity. (C)</p> Signup and view all the answers

What happens to amines at physiological pH regarding their bonding capabilities?

<p>They may ionize, enabling ionic bonding with target groups. (A)</p> Signup and view all the answers

How does the process of creating analogues from a lead compound assist in drug design?

<p>It helps pinpoint which structural modifications enhance effectiveness and reduce side effects. (B)</p> Signup and view all the answers

Which modification can be made to an amine to evaluate the importance of its binding in drug action?

<p>Converting it to an amide. (D)</p> Signup and view all the answers

Explain the significance of hydrogen bond donors (HBDs) and hydrogen bond acceptors (HBAs) in drug-target interactions.

<p>HBDs donate hydrogen atoms to form bonds, while HBAs accept them. This interaction is crucial for the specificity and strength of drug-target binding.</p> Signup and view all the answers

What is the purpose of identifying structure-activity relationships (SARs) in drug development?

<p>Identifying SARs helps researchers understand which chemical structures contribute to the desired biological activity of a drug. This knowledge guides modifications to enhance potency and reduce side effects.</p> Signup and view all the answers

How do ionic bonds influence the binding of drugs to their protein targets?

<p>Ionic bonds create strong electrostatic attractions between charged groups on the drug and its target, enhancing binding affinity. These interactions are particularly important in the context of proteins with charged residues.</p> Signup and view all the answers

Discuss the role of van der Waals interactions in the stability of drug-target complexes.

<p>Van der Waals interactions provide subtle but important stabilization to drug-target complexes due to their wide-ranging effects over short distances. While individually weak, they collectively contribute to the overall binding energy.</p> Signup and view all the answers

What are the main steps involved in the drug discovery process as outlined in Lecture 3?

<p>The drug discovery process includes choosing a disease, identifying a target, isolating lead compounds, determining their structures, and improving their interactions. This sequence leads to eventual clinical trials and market introduction.</p> Signup and view all the answers

How does the conversion of a drug to an amide form affect its ability to participate in hydrogen bonding?

<p>Conversion to an amide prevents the drug from acting as both a hydrogen bond donor and acceptor.</p> Signup and view all the answers

What effect does reducing a carbonyl group to an alcohol have on the drug's binding interactions?

<p>It alters the drug's geometry from planar sp2 hybrid to tetrahedral sp3 hybrid, which may disrupt dipole-dipole interactions.</p> Signup and view all the answers

Why are esters commonly used in drug design despite their rapid hydrolysis in the body?

<p>Esters are designed to mask polar groups, making them less polar for easier membrane penetration before being hydrolyzed.</p> Signup and view all the answers

In what way do aldehydes and ketones contribute to dipole-dipole interactions with drug targets?

<p>The polarized carbonyl groups in aldehydes and ketones create dipoles that interact with target molecules.</p> Signup and view all the answers

How does the role of the carbonyl oxygen differ when acting as a hydrogen bond acceptor?

<p>The carbonyl oxygen can accept hydrogen bonds, thus participating in critical drug-target interactions.</p> Signup and view all the answers

What is the consequence of converting a drug's carbonyl group into an ether on its binding ability?

<p>Conversion to an ether may impair the drug's capacity to act as a hydrogen bond acceptor due to increased distance.</p> Signup and view all the answers

How do hydrogen bonds influence the interactions between drugs and their target proteins?

<p>Hydrogen bonds stabilize the binding of drugs by providing specific interactions with target proteins.</p> Signup and view all the answers

What geometrical change occurs when a drug's carbonyl group is reduced, and how does this affect its interaction with the target?

<p>The reduction changes the molecule from a planar to a tetrahedral structure, potentially distancing it from effective binding with the target.</p> Signup and view all the answers

What is the significance of creating analogues of the lead compound in drug development?

<p>Creating analogues helps identify which parts of the molecule are necessary for binding and activity.</p> Signup and view all the answers

How can modifications to a drug's structure affect its biological activity?

<p>Modifications can either retain, enhance, or reduce the drug's activity, indicating the importance of specific functional groups.</p> Signup and view all the answers

What modifications can be made to aromatic groups to test their SAR in drug interactions?

<p>Aromatic groups can be changed to aliphatic groups to evaluate their structure-activity relationship (SAR).</p> Signup and view all the answers

Explain the concept of a pharmacophore in the context of drug design.

<p>A pharmacophore defines the key functional groups required for a drug's binding and biological activity.</p> Signup and view all the answers

How do carbonyl groups function in drug interactions?

<p>Carbonyl groups act as hydrogen bond acceptors (HBAs) in drug interactions.</p> Signup and view all the answers

What role do esters play in drug formulation?

<p>Esters are often used in the formation of prodrugs to enhance membrane permeability for drug absorption.</p> Signup and view all the answers

What role do hydrogen bond donors (HBDs) and acceptors (HBAs) play in drug interactions?

<p>HBDs and HBAs facilitate binding between drugs and their targets through hydrogen bonding.</p> Signup and view all the answers

Explain the significance of amines in drug interactions.

<p>Amines can form ionic bonds and hydrogen bonds, acting as both hydrogen bond donors (HBDs) and acceptors (HBAs).</p> Signup and view all the answers

Why is it important to convert amines to amides when testing drug binding?

<p>Converting amines to amides helps assess the significance of amine binding in the drug's interaction with its target.</p> Signup and view all the answers

Why is it important to identify functional groups in drug molecules?

<p>Identifying functional groups is crucial for predicting the drug's reactivity, solubility, and binding interactions with targets.</p> Signup and view all the answers

Describe how structure-activity relationships (SARs) are established.

<p>SARs are established by making small variations in the drug's structure and re-testing for biological activity.</p> Signup and view all the answers

How does the ionization state of amines influence their binding to drug targets?

<p>At physiological pH, ionized amines can form ionic bonds with negatively charged groups, enhancing binding.</p> Signup and view all the answers

What can be inferred if a modified drug structure shows reduced biological activity compared to the original?

<p>Reduced activity suggests that the modified functional group is important for binding and activity.</p> Signup and view all the answers

What defines a prodrug and how does it become active?

<p>A prodrug is an inactive compound that becomes active when metabolized in the body, typically through hydrolysis.</p> Signup and view all the answers

How do carboxylic acids participate in drug interactions?

<p>Carboxylic acids can participate in drug interactions through ionic bonding or hydrogen bonding, acting as both hydrogen bond donors (HBD) and acceptors (HBA).</p> Signup and view all the answers

What is the consequence of converting a carboxylic acid to an ester in drug chemistry?

<p>Converting a carboxylic acid to an ester eliminates its ability to participate in ionic bonding and reduces its hydrogen bonding capacity.</p> Signup and view all the answers

Describe the role of van der Waals forces in drug interactions.

<p>Van der Waals forces facilitate interactions between drug molecules and hydrophobic regions of their targets, aiding in binding.</p> Signup and view all the answers

What is the function of hydroxyl groups in alcohols and phenols regarding drug interactions?

<p>Hydroxyl groups enhance solubility and enable hydrogen bonding, thus improving the interaction between the drug and its target.</p> Signup and view all the answers

Why can ester linkages negatively impact a drug's ability to bind to its target?

<p>Ester linkages cannot form ionic bonds and cannot act as hydrogen bond donors, reducing the overall binding affinity of the drug.</p> Signup and view all the answers

In what way do alkenes and aromatics interact with target proteins?

<p>Alkenes and aromatics interact with target proteins primarily through van der Waals forces, engaging with hydrophobic regions.</p> Signup and view all the answers

What must occur for a prodrug to exert its therapeutic effects in the body?

<p>For a prodrug to exert its effects, it must undergo metabolic conversion, typically through hydrolysis or enzymatic action.</p> Signup and view all the answers

What is the primary effect of rigidification in drug design?

<p>Enhances selectivity for specific target proteins (C)</p> Signup and view all the answers

Which approach is central to target-oriented drug design?

<p>Designing drugs based on specific receptor targets (B)</p> Signup and view all the answers

What is typically found in the binding regions of a drug-target complex?

<p>A combination of various interaction types fine-tuning affinity (D)</p> Signup and view all the answers

How do ring variations in drug structure affect their pharmacological properties?

<p>They can alter the drug's solubility and stability (A)</p> Signup and view all the answers

What is one characteristic advantage of using isosteres in drug design?

<p>They can maintain biological activity while modifying unwanted properties (D)</p> Signup and view all the answers

Which of the following best describes the impact of metabolic stability on drug design?

<p>It affects both efficacy and safety of the drug (D)</p> Signup and view all the answers

Which of the following statements best describes isosteres?

<p>Molecules with similar size but different electronic distributions (D)</p> Signup and view all the answers

Which factor is most important when analyzing the economic cost of drug manufacturing?

<p>The ease of synthesis and yield of the drug (D)</p> Signup and view all the answers

In the context of drug action, how does the therapeutic window relate to dosage?

<p>It refers to the dose range between effective and toxic levels (A)</p> Signup and view all the answers

How does the presence of rotatable bonds affect a drug's flexibility?

<p>Allows for more structural variations (D)</p> Signup and view all the answers

What role does the hydrophilic/hydrophobic character of a drug play in its effectiveness?

<p>Determines its metabolic stability (B)</p> Signup and view all the answers

What is the significance of a diazepine ring system in drug design?

<p>Enhances drug potency and specificity (B)</p> Signup and view all the answers

Why is target-oriented drug design important in pharmacokinetics?

<p>It aims to optimize drug interactions with specific biological targets (D)</p> Signup and view all the answers

In what way do isosteres SH, NH2, and CH3 compare to OH?

<p>Similar in size but significantly differentiate in polarity (C)</p> Signup and view all the answers

What is the main benefit of using fixed bonds in drug design?

<p>They contribute to a more stable and predictable conformation (A)</p> Signup and view all the answers

What is the purpose of rigidification in drug design?

<p>To improve the stability of the drug-receptor interaction. (A)</p> Signup and view all the answers

Which of the following strategies is NOT commonly used in target-oriented drug design?

<p>Synthesizing unrelated molecules. (A)</p> Signup and view all the answers

In the context of target-oriented drug design, what is the significance of binding regions?

<p>They play a critical role in the interaction between drug and target. (B)</p> Signup and view all the answers

Which modification is typically involved in ring variations of drug structures?

<p>Changing the number of carbons in the ring. (A)</p> Signup and view all the answers

Which statement best describes isosteres in drug design?

<p>Isosteric modifications can affect the physico-chemical properties of the drug. (A)</p> Signup and view all the answers

What is a potential consequence of extending the structure of a drug?

<p>Enhanced interaction with unintended receptors. (D)</p> Signup and view all the answers

What effect does the variation of substituents have on drug efficacy?

<p>It can enhance or diminish binding affinity. (C)</p> Signup and view all the answers

In the context of drug design, why is ring fusion performed?

<p>To enhance binding interactions with target proteins. (A)</p> Signup and view all the answers

What is one advantage of designing isosteres?

<p>They can improve pharmacokinetic properties while mimicking original functional groups. (C)</p> Signup and view all the answers

Which of the following best defines ‘chain contractions’ in drug design?

<p>Shortening the length of a carbon chain to enhance efficacy. (A)</p> Signup and view all the answers

What is the effect of rigidification on a drug's conformation and its associated activity?

<p>Rigidification locks a drug into a more rigid conformation, increasing its activity and decreasing side effects.</p> Signup and view all the answers

How does the hydrophilic/hydrophobic character of a drug influence its pharmacokinetic behavior?

<p>The hydrophilic/hydrophobic character affects the drug's absorption, distribution, and elimination, influencing its overall bioavailability.</p> Signup and view all the answers

What role do isosteres play in drug design?

<p>Isosteres in drug design help to maintain similar size while altering polarity and electronic distribution for improved efficacy.</p> Signup and view all the answers

Why is metabolic stability an essential factor in designing effective drugs?

<p>Metabolic stability is crucial because it determines how long a drug remains active in the body before being broken down.</p> Signup and view all the answers

What is meant by rotatable bonds, and how do they impact a drug's flexibility?

<p>Rotatable bonds are bonds in a molecular structure that allow rotation, impacting the molecule's conformational flexibility.</p> Signup and view all the answers

What are the two phases of drug metabolism and their primary functions?

<p>Phase I involves oxidation, reduction, and hydrolysis, while Phase II includes conjugation reactions to make drugs more polar.</p> Signup and view all the answers

How does a drug's size play a role in its pharmacokinetic properties?

<p>A drug's size affects its ability to cross cell membranes, influencing absorption and distribution in the body.</p> Signup and view all the answers

Explain the significance of the therapeutic window in drug administration.

<p>The therapeutic window is the range between the effective dose and the dose that causes adverse effects.</p> Signup and view all the answers

Explain the importance of ionization in relation to drug absorption.

<p>Ionization affects a drug's solubility and permeability, both critical for its absorption in the gastrointestinal tract.</p> Signup and view all the answers

How did Thalidomide demonstrate the importance of drug isomerism in pharmacology?

<p>The R-enantiomer was effective for morning sickness, while the S-enantiomer caused severe birth defects.</p> Signup and view all the answers

What is the relationship between fixed bonds and the rigidity of a drug molecule?

<p>Fixed bonds restrict movement, contributing to the rigidity of a drug molecule and potentially enhancing its binding affinity.</p> Signup and view all the answers

What is the role of LD50 in toxicity testing?

<p>LD50 refers to the lethal dose required to kill 50% of the subjects tested.</p> Signup and view all the answers

What factors should be considered when manufacturing a drug, according to the content?

<p>Manufacturing considerations include ease of synthesis, economic costs, and safety.</p> Signup and view all the answers

Describe the potential consequences of forming toxic metabolites during drug metabolism.

<p>The formation of toxic metabolites can halt the progression of drug studies.</p> Signup and view all the answers

What is the primary difference between in vitro and in vivo toxicity testing?

<p>In vitro testing uses engineered cell cultures, while in vivo testing involves living organisms like lab animals.</p> Signup and view all the answers

What challenges can arise from using racemic mixtures in drug formulation?

<p>Racemic mixtures can include both beneficial and harmful isomers, complicating safety and efficacy.</p> Signup and view all the answers

What is the significance of identifying the pharmacophore in drug design?

<p>The pharmacophore identifies crucial functional groups required for drug activity and their spatial arrangement, simplifying complex lead compounds.</p> Signup and view all the answers

How does target-oriented drug design improve drug efficacy?

<p>Target-oriented drug design improves efficacy by creating analogues that enhance activity, reduce side effects, and facilitate easier administration.</p> Signup and view all the answers

What role do substituent variations play in drug design?

<p>Substituent variations can affect the steric fit and interactions of the drug with its target, influencing potency and selectivity.</p> Signup and view all the answers

Why are ring variations important in drug design?

<p>Ring variations can introduce additional binding sites and alter the drug's conformation, enhancing its interaction with target receptors.</p> Signup and view all the answers

Describe the role of isosteres in drug design.

<p>Isosteres are used to replace atoms or groups in a molecule to maintain similar properties while modifying biological activity.</p> Signup and view all the answers

How can chain extensions or contractions impact drug design?

<p>Chain extensions or contractions can strengthen or weaken interactions with the receptor, consequently improving or diminishing drug efficacy.</p> Signup and view all the answers

Explain how the concept of a pharmacophore aids in simplifying lead compounds.

<p>By identifying key functional groups and their arrangement, the pharmacophore allows for the reduction of complex natural products into simpler, more amenable drug candidates.</p> Signup and view all the answers

What is the importance of understanding drug metabolites during drug design?

<p>Understanding drug metabolites is essential to predict the drug's pharmacokinetic behavior and potential toxicity.</p> Signup and view all the answers

Discuss the impact of synthetic challenges in drug manufacturing on drug design.

<p>Synthetic challenges can limit the feasibility of creating certain drug analogues, impacting the design choices made during drug development.</p> Signup and view all the answers

How do clinical trials relate to the overall drug design process?

<p>Clinical trials assess the safety and efficacy of the designed drug in humans, providing critical feedback that can inform future modifications and developments.</p> Signup and view all the answers

Which of the following factors contributes to poor drug absorption according to Lipinski's Rule of Five?

<p>More than 5 H-bond acceptors (A)</p> Signup and view all the answers

What distinguishes a pharmacophore in drug design?

<p>It outlines key functional groups responsible for biological activity. (C)</p> Signup and view all the answers

Which bonding force is primarily responsible for stabilizing tertiary protein structure?

<p>Hydrophobic interactions (B)</p> Signup and view all the answers

Which of the following statements about hydrogen bonding in drug interactions is correct?

<p>Hydrogen bonds can be formed between drug functional groups and protein targets. (B)</p> Signup and view all the answers

What is indicated by a log P value greater than 5 in drug properties?

<p>Likely poor absorption (A)</p> Signup and view all the answers

Which of the following statements best describes Lipinski's Rule of Five?

<p>It outlines five specific criteria that determine a drug's solubility and permeability. (C)</p> Signup and view all the answers

What is the primary function of a pharmacophore in drug design?

<p>To identify the specific structural features necessary for biological activity. (C)</p> Signup and view all the answers

Which of the following forces plays a significant role in maintaining protein structure?

<p>Ionic interactions and hydrogen bonds are crucial for protein conformations. (A)</p> Signup and view all the answers

In the context of drug-target interactions, what role do hydrogen bond donors and acceptors play?

<p>They facilitate reversible interactions, enhancing binding affinity. (B)</p> Signup and view all the answers

What is the implication of having more than 10 H-bond acceptors in a drug molecule?

<p>It decreases the likelihood of good absorption and permeation. (D)</p> Signup and view all the answers

What are Lipinski's Rule of Five parameters, and why are they important in drug design?

<p>Lipinski's Rule of Five includes molecular weight under 500, log P under 5, fewer than 5 H-bond donors, and fewer than 10 H-bond acceptors. These parameters help predict drug absorption and permeability.</p> Signup and view all the answers

Define a pharmacophore and its significance in drug discovery.

<p>A pharmacophore is a set of functionalities responsible for the biological activity of a drug molecule. It guides the design of new compounds by highlighting essential features for target interaction.</p> Signup and view all the answers

Differentiate between hydrogen bond donors and acceptors in the context of drug-target interactions.

<p>Hydrogen bond donors are molecules that provide a hydrogen atom, usually with an attached electronegative atom like oxygen or nitrogen, while acceptors are typically electronegative atoms that can attract hydrogen atoms. This distinction is crucial for understanding how drugs bind to their targets.</p> Signup and view all the answers

Discuss the importance of protein structure in understanding drug interactions.

<p>Protein structure determines the shape and functionality of the protein, influencing how drugs interact with specific sites. Understanding the structure helps in predicting the efficacy and selectivity of drug actions.</p> Signup and view all the answers

What factors influence the strength of intermolecular forces between drugs and their target proteins?

<p>The strength of intermolecular forces is influenced by the types of bonds (ionic, hydrogen, van der Waals) and the spatial arrangement of functional groups on both the drug and target protein. These interactions dictate binding affinity and specificity.</p> Signup and view all the answers

What are the implications of violating Lipinski's Rule of Five for drug absorption?

<p>Violating Lipinski's Rule of Five can lead to poor absorption and permeability, making it challenging for drugs to be effectively delivered in the body.</p> Signup and view all the answers

How do hydrogen bond donors and acceptors influence drug-target interactions?

<p>Hydrogen bond donors and acceptors play critical roles in stabilizing drug-target interactions by facilitating specific bonding that enhances binding affinity.</p> Signup and view all the answers

Define a pharmacophore and its importance in drug design.

<p>A pharmacophore is a set of structural features that are necessary for the biological activity of a drug, guiding the development of new therapeutic agents.</p> Signup and view all the answers

Discuss the relationship between protein structure and drug efficacy.

<p>The efficacy of a drug is closely related to its ability to interact with the three-dimensional structure of its target protein, influencing binding and subsequent biological response.</p> Signup and view all the answers

What is the significance of functional groups in the context of drug interactions?

<p>Functional groups determine the chemical behavior of drug molecules, influencing their solubility, reactivity, and interactions with biological targets.</p> Signup and view all the answers

Which factor is likely to lead to poor absorption of a drug via oral administration?

<p>More than 10 H-bond acceptors (C)</p> Signup and view all the answers

What type of bonds primarily governs the solubility and permeability of drug molecules?

<p>Hydrogen bonds (A)</p> Signup and view all the answers

In the context of Structure-Activity Relationships (SAR), what does SAR help design?

<p>More potent analogues of existing drugs (D)</p> Signup and view all the answers

Which statement accurately reflects Lipinski’s Rule of Five regarding drug absorption?

<p>Fewer than 5 H-bond donors are beneficial for absorption. (D)</p> Signup and view all the answers

What is the effect of increasing molecular weight on drug absorption?

<p>It generally hampers absorption. (C)</p> Signup and view all the answers

Which of the following contributes to poor absorption of drugs in relation to hydrogen bonding?

<p>Excessive H-bond donors (D)</p> Signup and view all the answers

Why are drugs designed with fewer H-bond donors generally more successful in oral absorption?

<p>They tend to permeate membranes better. (D)</p> Signup and view all the answers

What is a common characteristic of drugs that are exceptions to Lipinski's Rule of Five?

<p>They treat specific disorders like gut conditions. (C)</p> Signup and view all the answers

What must a compound primarily be able to do to successfully cross a membrane?

<p>Be soluble in lipid and water. (D)</p> Signup and view all the answers

According to Lipinski's Rule of Five, what percentage of compounds is typically successful with a molecular weight greater than 500 g/mol?

<p>11% (B)</p> Signup and view all the answers

Which property of a drug significantly impacts its ability to cross lipid membranes?

<p>Hydrophobicity level from Log P values. (C)</p> Signup and view all the answers

What is the relationship between hydrogen bond donors and acceptors in drug molecules?

<p>Donors usually include N, O or F atoms. (B)</p> Signup and view all the answers

What does a Log P value greater than 5 indicate regarding a compound's physical properties?

<p>It is very hydrophobic and likely to be trapped in membranes. (B)</p> Signup and view all the answers

What is a significant drawback of a drug having too many hydrogen bonds?

<p>It will not pass lipid membranes effectively. (A)</p> Signup and view all the answers

Which of the following is a key factor in determining the oral bioavailability of a drug?

<p>Molecular weight and solubility. (D)</p> Signup and view all the answers

According to Lipinski's findings, what percentage of compounds show more than 10 hydrogen bonds in their structure?

<p>12% (C)</p> Signup and view all the answers

How do alkyl substituents influence drug design in relation to hydrophobic pockets?

<p>They can probe the hydrophobic pocket's dimensions. (D)</p> Signup and view all the answers

What is the significance of hydrogen bonding groups in the modification of a drug's structure?

<p>They help in altering acidity and basicity of the molecule. (A)</p> Signup and view all the answers

Which of the following factors is essential when applying Lipinski's Rule of Five in drug design?

<p>Fewer than five hydrogen bond donors and acceptors. (B)</p> Signup and view all the answers

What effect do aromatic substituents have on drug molecules?

<p>They can alter the potency by affecting hydrogen bonding. (A)</p> Signup and view all the answers

How does molecular weight impact the characteristics of drugs in relation to Lipinski's Rule?

<p>Lower molecular weight improves solubility and permeability. (B)</p> Signup and view all the answers

In the context of drug binding, what is the primary role of weak hydrogen bonds?

<p>They are crucial for the initial drug recognition process. (A)</p> Signup and view all the answers

Which strategy is used to optimize drugs for effectiveness and selectivity?

<p>Making small, iterative changes to drug structures. (B)</p> Signup and view all the answers

Why is it challenging to transition from bench to plant in drug development?

<p>Lead compounds often have low activity and significant side effects. (D)</p> Signup and view all the answers

What does the term 'serendipity' refer to in scientific discoveries?

<p>It refers to the accidental discovery of something fortunate while searching for something else.</p> Signup and view all the answers

How did Louis Pasteur's quote relate to the role of chance in scientific observation?

<p>His quote suggests that chance favors those who are prepared to observe and recognize important findings.</p> Signup and view all the answers

What was the initial purpose of the drug Clonidine before it was discovered to lower blood pressure?

<p>Clonidine was initially designed to be a nasal vasoconstrictor for nasal drops and shaving soaps.</p> Signup and view all the answers

Describe the significance of disulfiram in the treatment of chronic alcoholism.

<p>Disulfiram induces an acute sensitivity to alcohol, helping to deter consumption in individuals with alcoholism.</p> Signup and view all the answers

What are the implications of Lipinski's Rule of Five for drug development?

<p>Lipinski's Rule of Five identifies key molecular characteristics important for the oral bioavailability of drugs.</p> Signup and view all the answers

How did Albert Hofmann's discovery of LSD exemplify serendipity in drug research?

<p>His discovery was accidental but rooted in systematic pharmaceutical research and experiments.</p> Signup and view all the answers

What role does the history of mustard gas exposure play in understanding leukemia proliferation?

<p>Survivors of mustard gas exposure lost their white blood cells' natural defenses, leading to the study of leukemia's cell proliferation.</p> Signup and view all the answers

Why are observations made during clinical trials critical for drug discovery?

<p>Clinical trials reveal unexpected properties and effects of drugs, leading to potential new applications.</p> Signup and view all the answers

What is the IUPAC definition of a pharmacophore?

<p>A pharmacophore is defined as an ensemble of steric and electronic features necessary for optimal interactions with a biological target to trigger or block biological responses.</p> Signup and view all the answers

Explain the concept of QSAR in medicinal chemistry.

<p>QSAR, or quantitative structure-activity relationship, is the process of quantitatively correlating chemical structure with specific biological activity or chemical reactivity.</p> Signup and view all the answers

What is the primary goal of lead optimisation in drug development?

<p>The primary goal of lead optimisation is to improve drug efficacy, focusing on stability and bioavailability towards developing effective pro-drugs.</p> Signup and view all the answers

How do pro-drugs function in the body?

<p>Pro-drugs undergo chemical transformation in the bloodstream or specific tissues to release biologically active metabolites, which are the actual therapeutic agents.</p> Signup and view all the answers

Describe the significance of Log P values in evaluating drug properties.

<p>Log P values indicate the lipophilicity of a compound, which influences its permeability, bioavailability, and potential distribution within the body.</p> Signup and view all the answers

What must a compound be in order to effectively cross biological membranes?

<p>A compound must be both soluble in water and lipid to cross membranes effectively.</p> Signup and view all the answers

Why is the study of structure-activity relationships (SAR) important in medicinal chemistry?

<p>SAR studies are important because they help in understanding how changes in chemical structure impact biological activity, aiding in the design of better therapeutic agents.</p> Signup and view all the answers

What is the significance of a Log P value above 5 in drug molecules?

<p>A Log P value above 5 indicates that the compound is very hydrophobic, which can lead to it being trapped in membranes.</p> Signup and view all the answers

What role does the liver play in the metabolism of drugs?

<p>The liver metabolizes drugs, helping to convert them into their active or inactive forms, which affects their bioavailability and elimination from the body.</p> Signup and view all the answers

Explain the relationship between steric features and target interactions in pharmacophore development.

<p>Steric features in a pharmacophore influence how effectively a drug's shape and size can interact with its biological target, impacting binding and overall efficacy.</p> Signup and view all the answers

According to Lipinski's rules, what relationship do hydroxyl (OH) and amine (NH) groups have with hydrogen bonding?

<p>Hydroxyl and amine groups act as hydrogen bond donors in drug molecules.</p> Signup and view all the answers

What is the impact of excessive hydrogen bonding within a drug molecule?

<p>Excessive hydrogen bonding can hinder a drug's ability to pass through lipid membranes.</p> Signup and view all the answers

How do electron donating substituents affect chemical derivatisation?

<p>Electron donating substituents enhance nucleophilicity, allowing for more efficient chemical modifications.</p> Signup and view all the answers

What is the significance of hydrophobic pockets in drug design?

<p>Hydrophobic pockets interact with alkyl substituents, influencing the drug's binding affinity and specificity.</p> Signup and view all the answers

Why is the molecular weight of a compound important for oral drug delivery?

<p>Compounds with a molecular weight greater than 500 g/mol are less likely to be successful in oral delivery.</p> Signup and view all the answers

Why is it important to consider Lipinski's Rule of Five in drug development?

<p>Lipinski's Rule of Five helps predict the oral bioavailability of drug candidates, guiding the optimization process.</p> Signup and view all the answers

What constitutes a successful drug based on Lipinski's findings regarding hydrogen bonding?

<p>Successful drugs typically have fewer than 10 hydrogen bonds in their molecular structure.</p> Signup and view all the answers

What role do aromatic substituents play in modifying drug potency?

<p>Aromatic substituents can adjust acidity and basicity, thereby modulating the strength of hydrogen bonds.</p> Signup and view all the answers

How does the partition coefficient (P) help in understanding the solubility of a drug?

<p>The partition coefficient (P) is the ratio of a drug's concentration in octanol to its concentration in water, indicating its solubility.</p> Signup and view all the answers

What limitation exists for drug compounds that have a high tendency to self-bond?

<p>Compounds that bond too strongly to themselves cannot easily pass lipid membranes.</p> Signup and view all the answers

How does variation in substituent size influence drug interactions?

<p>Changing substituent size affects steric hindrance, potentially altering binding strength within the target site.</p> Signup and view all the answers

Can you describe the impact of further heteroatoms in drug molecules?

<p>Incorporating heteroatoms can enhance solubility and modify the electronic properties of the molecule.</p> Signup and view all the answers

What is the primary challenge encountered when moving from bench to plant in drug development?

<p>The primary challenge is achieving consistent activity and stability due to scale-up processes.</p> Signup and view all the answers

Why is it often necessary to create analogues of lead compounds?

<p>Lead compounds frequently have low activity, poor selectivity, or significant side effects, necessitating modifications.</p> Signup and view all the answers

What is the significance of Lipinski’s Rule of Five in drug absorption?

<p>Lipinski’s Rule of Five helps to predict the likelihood of poor absorption of drug candidates based on their molecular properties, guiding drug design.</p> Signup and view all the answers

Describe the main criteria set by Lipinski’s Rule of Five regarding hydrogen bond donors and acceptors.

<p>Lipinski’s Rule states that more than 5 H-bond donors and more than 10 H-bond acceptors are likely to hinder drug absorption.</p> Signup and view all the answers

How did Paul Ehrlich contribute to the field of medicinal chemistry?

<p>Paul Ehrlich is known as the 'Father of Chemotherapy' for developing the first effective medicinal treatment for syphilis.</p> Signup and view all the answers

What does the term 'structure activity relationship' (SAR) refer to in drug design?

<p>SAR refers to the relationship between the chemical structure of a molecule and its biological activity, guiding modifications for improved efficacy.</p> Signup and view all the answers

Explain how modifying the structure of butylbenzene could enhance its polarity.

<p>To enhance polarity, one could shorten the alkyl chain or add a methoxy (-OCH3) group to the para position of the ring.</p> Signup and view all the answers

Why are exceptions to Lipinski’s Rule of Five noted for certain drug types?

<p>Certain drug types, like antibiotics and medications for gut disorders, can exceed these parameters while still being effective due to their delivery methods.</p> Signup and view all the answers

What is the relationship between log P and drug absorption as stated in Lipinski’s Rule?

<p>A log P value over 5 indicates that poor absorption is likely, as it suggests high lipophilicity which may hinder solubility.</p> Signup and view all the answers

How can rejection of certain molecular characteristics in drug candidates improve drug efficacy?

<p>Rejecting candidates that do not meet Lipinski’s Rule can streamline the drug discovery process to focus on those that are more likely to be absorbed effectively.</p> Signup and view all the answers

What is the significance of the pharmacophore in drug development?

<p>The pharmacophore is crucial as it defines the necessary steric and electronic features required for effective interaction with biological targets.</p> Signup and view all the answers

Explain the purpose of lead optimization in medicinal chemistry.

<p>Lead optimization aims to enhance a drug's efficacy by improving its stability and bioavailability through modifications to its chemical structure.</p> Signup and view all the answers

What role do pro-drugs play in pharmacology?

<p>Pro-drugs are designed to undergo transformation in the body, releasing active metabolites that exert the desired therapeutic effect.</p> Signup and view all the answers

How does quantitative structure-activity relationship (QSAR) contribute to drug design?

<p>QSAR quantitatively correlates chemical structures with their biological activities, providing a predictive framework for designing more effective drugs.</p> Signup and view all the answers

What is the relationship between Log P values and drug solubility?

<p>Log P values indicate a compound's hydrophilicity or lipophilicity; higher Log P often correlates with increased membrane permeability, thus affecting solubility.</p> Signup and view all the answers

Why is it essential to make further analogues of lead compounds in drug discovery?

<p>It is essential because most lead compounds often have low activity, poor selectivity, and significant side effects.</p> Signup and view all the answers

In the context of structure activity relationships (SAR), why is the modification of chemical structures important?

<p>Modifying chemical structures can enhance therapeutic properties while minimizing side effects, leading to more effective drugs.</p> Signup and view all the answers

How do alkyl substituents affect drug design in relation to hydrophobic pockets?

<p>Alkyl substituents can interact with hydrophobic pockets, and varying their length and bulk can help probe the pocket's depth and width.</p> Signup and view all the answers

How can the structure of benzylpenicillin illustrate concepts of drug activity?

<p>Benzylpenicillin's structure exemplifies how specific functional groups and their arrangements influence antibacterial efficacy.</p> Signup and view all the answers

What role do aromatic substituents play in modifying the properties of a drug molecule?

<p>Aromatic substituents can alter the basicity and acidity of the molecule, as well as the positioning of hydrogen bonding groups which may enhance potency.</p> Signup and view all the answers

Why might high Log P values be associated with a lower solubility in aqueous environments?

<p>High Log P values indicate greater lipophilicity, which can reduce a compound's solubility in water, affecting absorption and distribution.</p> Signup and view all the answers

What is Lipinski's Rule of Five, and why is it important in drug design?

<p>Lipinski's Rule of Five is a set of guidelines that helps predict good molecular drug characteristics such as solubility and permeability.</p> Signup and view all the answers

In what way can small iterative changes to drug structure benefit drug development?

<p>Small iterative changes can optimize molecules for effectiveness, safety, solubility, and selectivity.</p> Signup and view all the answers

Why are imidazo[1-5a]pyridines significant in drug derivatization?

<p>Imidazo[1-5a]pyridines serve as versatile scaffolds that can accommodate various substituents for enhanced biological activity.</p> Signup and view all the answers

How can the position of hydrogen bonding groups around a ring affect drug activity?

<p>Changing the position of hydrogen bonding groups can increase drug potency by improving interactions with biological targets.</p> Signup and view all the answers

What factors must be considered when varying substituents in drug molecules?

<p>Factors include the length, bulk, and type of substituents, as well as their interactions with specific binding sites.</p> Signup and view all the answers

What are the four key parameters of Lipinski's Rule of Five that indicate poor absorption?

<p>Molecular weight over 500, log P over 5, more than 5 H-bond donors, and more than 10 H-bond acceptors.</p> Signup and view all the answers

How can understanding Structure Activity Relationships (SAR) aid in drug design?

<p>SAR helps in identifying the relationship between a drug's chemical structure and its biological activity, guiding modifications for improved efficacy.</p> Signup and view all the answers

What exceptions exist for Lipinski's Rule of Five in drug delivery?

<p>Non-oral route drugs, drugs for gut disorders, antibiotics, antifungals, vitamins, and cardiac glycosides are exceptions.</p> Signup and view all the answers

What is the primary benefit of using the 'magic bullet' approach in chemotherapy as proposed by Paul Ehrlich?

<p>It allows for targeted treatment of diseases while minimizing damage to healthy cells.</p> Signup and view all the answers

Why is it essential to shorten the alkyl chain or modify the structure in drug design?

<p>Altering the structure can improve the drug's polarity, leading to better solubility and absorption.</p> Signup and view all the answers

In the context of drug interactions, what role do H-bond donors and acceptors play?

<p>H-bond donors provide protons while acceptors can stabilize the binding interactions between the drug and its target.</p> Signup and view all the answers

What does a log P value exceeding 5 indicate about a compound's absorption?

<p>It suggests that the compound is more lipophilic, which may lead to poor absorption in aqueous environments.</p> Signup and view all the answers

What is the significance of the number of hydrogen bond donors and acceptors in drug design?

<p>They influence a drug's solubility and ability to permeate biological membranes, affecting bioavailability.</p> Signup and view all the answers

What are the key factors that influence a compound's ability to pass through the gut and into the bloodstream?

<p>The key factors include size, solubility, and hydrogen bonding capabilities of the compound.</p> Signup and view all the answers

How does the molecular weight of a compound affect its success for oral delivery?

<p>Compounds with molecular weights greater than 500 g/mol are less successful for oral delivery as they tend to have poor membrane permeability.</p> Signup and view all the answers

What is Log P and why is it important for drug solubility?

<p>Log P is the partition coefficient (octanol/water) that indicates a compound's hydrophobicity and is crucial for determining its solubility in both water and lipid environments.</p> Signup and view all the answers

What did Lipinski's rule of five suggest about hydrogen bonding in drug compounds?

<p>Lipinski's rule suggests that drug compounds should ideally possess no more than 5 hydrogen bond donors and ideally not more than 10 hydrogen bond acceptors to enhance permeability.</p> Signup and view all the answers

Explain the role of hydrogen bond donors and acceptors in drug absorption.

<p>Hydrogen bond donors, such as OH and NH groups, provide the ability to interact with target molecules, while acceptors like O and N are essential for forming these interactions.</p> Signup and view all the answers

Why is it important for a drug compound to be neither too soluble in water nor in lipids?

<p>If a compound is too soluble in water, it may not cross lipid membranes well, and if too soluble in lipids, it may get trapped in membranes, preventing absorption.</p> Signup and view all the answers

How do the properties of compounds with high Log P values impact their behavior in the body?

<p>Compounds with high Log P values are very hydrophobic, which can cause them to stick to membranes and hinder their ability to cross them.</p> Signup and view all the answers

What percentage of compounds in Lipinski’s database had more than 10 hydrogen bonds, and what does this imply?

<p>Only 12% of the compounds had more than 10 hydrogen bonds, implying that excessive hydrogen bonding can limit a compound's efficacy in absorption.</p> Signup and view all the answers

What is serendipity and how does it relate to scientific discoveries?

<p>Serendipity is the accidental discovery of something fortunate while looking for something else. It highlights how chance encounters can lead to significant scientific advancements.</p> Signup and view all the answers

Discuss the significance of Louis Pasteur's quote in the context of research.

<p>Louis Pasteur's quote suggests that while chance may provide opportunities, only those who are prepared can effectively capitalize on them. This underscores the importance of thorough research and systematic experimentation.</p> Signup and view all the answers

Explain how disulfiram was discovered and its primary use.

<p>Disulfiram was discovered when rubber industry workers found they developed a distaste for alcohol due to an antioxidant exposure. It is primarily used to treat chronic alcoholism by causing an acute sensitivity to alcohol.</p> Signup and view all the answers

What was the original purpose of clonidine and how was it repurposed?

<p>Clonidine was originally designed as a nasal vasoconstrictor, but clinical trials revealed its ability to lower blood pressure. It became an important antihypertensive medication due to this unexpected effect.</p> Signup and view all the answers

How did sildenafil's original intent differ from its eventual use?

<p>Sildenafil was initially developed as a heart treatment to act as a vasodilator, but it gained popularity as a treatment for erectile dysfunction. This shift in use showcases the unpredictable nature of drug applications.</p> Signup and view all the answers

What is Lipinski's Rule of Five and why is it important?

<p>Lipinski's Rule of Five is a set of criteria that helps predict the oral bioavailability of drug-like compounds based on their molecular characteristics. It is important in drug development as it guides the selection of viable drug candidates.</p> Signup and view all the answers

What unique feature does serendipity bring to the discovery of pharmaceuticals?

<p>Serendipity contributes an element of surprise and innovation in pharmaceutical discovery, as it can lead to novel uses for existing compounds. This unexpected exploration often results in breakthroughs that structured research may overlook.</p> Signup and view all the answers

How did the accidental ingestion of LSD illustrate the concept of serendipity in scientific discovery?

<p>Albert Hofmann’s accidental ingestion of LSD during a lab experiment led to the discovery of its psychoactive properties, emphasizing how unplanned events can result in significant scientific revelations. This reinforces the unpredictable nature of drug discovery.</p> Signup and view all the answers

Flashcards

Drug interactions

Drugs interact with specific targets in the body to trigger a biological response.

Functional groups in drugs

Specific groups of atoms within a drug molecule that dictate its chemical properties, such as solubility, reactivity and ionisation.

Predicting drug properties

Identifying functional groups allows for predicting how a drug will behave in the body, including absorption and potential activity.

Drug administration routes

Drugs can be administered in different ways, including swallowing, injection, inhalation, application, and insertion.

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Drug target

A specific molecule in the body that a drug interacts with to produce a biological effect.

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Drug Absorption Mechanisms

Methods by which a drug enters the bloodstream after administration; includes passive diffusion, facilitated diffusion, active transport, and pinocytosis.

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Passive Diffusion

Drug movement across cell membranes from an area of high concentration to low concentration without energy input.

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Facilitated Diffusion

Drug movement across cell membranes with the help of a carrier protein; still no energy input required.

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Active Transport

Drug movement across cell membranes against a concentration gradient; requires energy input from the cell.

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Proteins as Drug Targets

Many drug targets are proteins, often found in cell membranes, and only specific parts of the proteins interact with the drug.

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Drug Distribution

The process by which a drug moves from the bloodstream to the tissues after absorption.

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Drug Metabolism (Biotransformation)

Chemical alteration of a drug by the body (usually liver), often to make it easier to excrete.

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Primary Structure

The linear sequence of amino acids in a protein, linked by peptide bonds.

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Secondary Structure

Local folding patterns of a polypeptide chain, stabilized by hydrogen bonds. Examples include alpha-helices and beta-sheets.

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Tertiary Structure

The overall three-dimensional shape of a protein, determined by interactions between amino acid side chains. Crucial for function and drug binding.

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Forces in Tertiary Structure

Interactions between amino acid side chains that contribute to the tertiary structure: covalent, ionic, hydrogen, and van der Waals forces.

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Drug-Target Interactions

The binding of a drug to its target, usually involving non-covalent forces like hydrogen bonding, ionic interactions, and van der Waals interactions.

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Covalent Bonding in Drug-Target Interactions

A strong and usually irreversible interaction between a drug and its target, often involving the formation of a new chemical bond.

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Drug Targets Beyond Proteins

Drugs can also target molecules other than proteins, such as nucleic acids (DNA and RNA), lipids, and carbohydrates.

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Drug's effect on the body

Drugs work by interacting with specific targets in the body, like proteins, to trigger a biological response.

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Predicting drug absorption

Knowing a drug's functional groups helps predict how it will be absorbed into the body, for example, whether it can pass through cell membranes.

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Drug interaction with target

The drug binds to a specific target, like a key fitting into a lock, triggering a biological response.

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Forces in protein structure

Proteins are complex molecules held together by various forces, like hydrogen bonds, ionic interactions, and van der Waals forces.

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Protein Primary Structure

The linear sequence of amino acids in a protein, linked by peptide bonds. It's like the alphabet of the protein.

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Protein Secondary Structure

Local folding patterns of a polypeptide chain, stabilized by hydrogen bonds. Examples include alpha-helices and beta-sheets.

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Protein Tertiary Structure

The overall three-dimensional shape of a protein, determined by interactions between amino acid side chains. Crucial for function and drug binding.

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What forces stabilize tertiary structure?

Interactions between amino acid side chains that contribute to the tertiary structure: covalent, ionic, hydrogen, and van der Waals forces.

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Ionic Bonds in Drug Targets

Ionic bonds occur between negatively charged groups on targets, like carboxylate ions from aspartic or glutamic acid, and positively charged groups on drugs. These bonds are relatively strong, contributing to drug-target interactions.

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Ion-Dipole and Dipole-Dipole Interactions

These weak interactions involve attractions between polar molecules (like water) and charged ions or other polar molecules. They are weaker than ionic bonds, but still play a role in drug-target interactions, especially involving functional groups with electronegative atoms.

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Hydrogen Bonding in Targets

Stronger than other weak interactions, hydrogen bonds occur between a hydrogen atom covalently bonded to an electronegative atom (like oxygen or nitrogen) and another electronegative atom on a nearby molecule. These bonds often involve functional groups like OH and NH.

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Hydrogen Bond Donor & Acceptor

The molecule with the hydrogen covalently bonded to an electronegative atom (like OH) is the hydrogen bond donor. The molecule with the electronegative atom that accepts the hydrogen bond is the acceptor.

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Importance of Hydrogen Bonding

Hydrogen bonds are vital for drug-target interactions as they contribute to the strength and specificity of these interactions.

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Alcohols & Phenols in Drugs

These common functional groups in drugs participate in hydrogen bonding, influencing their interactions with targets.

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Salicylic Acid's Interactions

Salicylic acid, a common drug, utilizes hydrogen bonding for interactions with its target, involving its OH and COOH groups.

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Strength of Drug-Target Interactions

The strength of interactions depends on the type of bond. Ionic bonds are strongest, followed by hydrogen bonds, and then by van der Waals forces.

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Active Site

The specific region on a target molecule where a drug binds to produce a biological effect.

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Covalent Bond

The strongest type of bond formed when two atoms share electrons. This is generally irreversible and often involves drug modifications.

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What is the key difference between covalent and ionic bonds?

Covalent bonds involve sharing electrons, while ionic bonds involve the transfer of electrons resulting in attraction between oppositely charged ions.

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Ionic Bond

An electrostatic interaction between oppositely charged ions. These bonds are weaker than covalent bonds but play a crucial role in drug-target interactions.

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Hydrogen Bond

A weak interaction between a hydrogen atom covalently bonded to an electronegative atom (like oxygen or nitrogen) and an electron pair in a close by atom.

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Hydrogen Bond Donors/Acceptors

Donors have a hydrogen atom attached to an electronegative atom (like oxygen or nitrogen), while acceptors have a lone pair of electrons.

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What are the functional groups important for hydrogen bonding?

Groups with O-H or N-H bonds are typically donors, while groups with lone pairs on O or N are acceptors.

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Bond Strength

The strength of a bond is determined by the energy needed to break it. Bonds with higher energy are stronger and more stable.

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HBD

Hydrogen bond donor, a molecule with a hydrogen atom covalently bonded to an electronegative atom like oxygen or nitrogen, able to donate a hydrogen bond to another molecule.

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HBA

Hydrogen bond acceptor, a molecule with an electronegative atom like oxygen or nitrogen able to accept a hydrogen bond from another molecule.

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How can you modify an OH group to see if it contributes to binding?

Change the OH group to an ether or an ester functional group. This allows you to test if the OH group was acting as a HBD or HBA, and if its presence is essential for binding.

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What can't ethers do?

Ethers can't act as HBDs because the oxygen atom has no hydrogen atom to donate. They are also poor HBAs due to steric hindrance.

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London Dispersion Forces

Weak, temporary attractions between non-polar molecules, arising from fluctuations in electron distribution.

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What types of molecules are London forces important for?

They are important for molecules containing aromatic rings or alkyl groups (aliphatic side chains).

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How do drugs often interact with targets?

Drugs typically interact with targets through multiple interactions, involving various forces like hydrogen bonding, ionic interactions, and van der Waals interactions.

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Importance of drug-target interactions

Drug-target interactions are essential for drug efficacy and safety. They determine how a drug binds to its target and triggers a biological response.

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Hydrogen Bond Donors (HBD)

Molecules with a hydrogen atom attached to an electronegative atom like oxygen or nitrogen, able to donate a hydrogen bond.

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Hydrogen Bond Acceptors (HBA)

Molecules with an electronegative atom like oxygen or nitrogen able to accept a hydrogen bond from another molecule (HBD).

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Alcohols and Phenols

Alcohols and phenols are common functional groups in drugs. These are usually involved in forming hydrogen bonds with the target.

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Drug-Target Interaction Strength

The strength of the interaction depends on the type of bond involved. Ionic bonds are the strongest, followed by hydrogen bonds, then van der Waals interactions.

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Ethers & HBDs

Ether functional groups cannot act as HBDs because the oxygen atom does not have a hydrogen atom to donate.

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Ethers & HBAs

Ethers are poor HBAs due to 'steric hindrance', meaning their bulky structure blocks the oxygen atom from readily accepting a hydrogen bond.

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Modifying an OH Group

Changing an OH group to an ether or an ester functional group helps determine if the OH group was acting as a HBD or HBA and if it was essential for drug binding.

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Importance of Multiple Interactions

Drugs often bind to their targets through multiple interactions, increasing the strength and specificity of the binding.

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What are SARs?

SARs (Structure-Activity Relationships) is the process of studying how small changes in a drug's structure affect its activity and ability to bind to a target.

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How do amines interact with targets?

Amines can interact with targets through ionic bonds due to their positive charge and through hydrogen bonding, as they can act as both hydrogen bond donors (HBDs) and acceptors (HBAs).

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What's the role of carbonyl groups?

Carbonyl groups act as hydrogen bond acceptors (HBAs), meaning they can accept a hydrogen bond from another molecule.

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Why are esters used in prodrugs?

Esters are often used in the formation of prodrugs because they can help a drug to cross membranes more easily. This helps the drug reach its target.

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How do you test aromatic group SAR?

You test the SAR of aromatic groups (rings) by changing them to aliphatic groups (chains). This helps determine if the aromatic group is essential for binding.

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Lead compound

The initial drug molecule that exhibits biological activity against a target, but may have limitations like weak activity or undesirable side effects.

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Pharmacophore

The essential features of a drug molecule that are vital for binding to and interacting with its target, typically consisting of specific functional groups.

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Structure-Activity Relationships (SARs)

The study of how changes in the structure of a drug molecule affect its biological activity, helping identify important functional groups and optimize drug design.

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Amine as HBD/HBA

Amines can act as both hydrogen bond donors (HBDs) and acceptors (HBAs) depending on their ionization state and structure. In their protonated form, they can ionically bond with COOH groups.

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Testing Amine Binding

To determine if amine binding is essential for drug activity, convert the amine group to an amide. If activity drops, the amine was important.

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HBD & HBA in Drug Binding

Hydrogen bond donors and acceptors play a crucial role in drug-target interactions. Understanding their involvement helps optimize drug design.

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Impact of Functional Group Modification

Changing functional groups, like converting an OH group to an ether or ester, allows you to investigate their roles in binding and activity.

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Multiple Interactions in Drug Binding

Drugs often interact with their targets through multiple interactions, including hydrogen bonding, ionic bonds, and van der Waals forces. These multiple interactions enhance binding strength and specificity.

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Prodrugs

Compounds that are inactive themselves but are converted to active drugs within the body through metabolic processes. They often have improved properties like better solubility, faster absorption, or better stability.

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Ester Hydrolysis

The breakdown of an ester bond in a prodrug by water molecules, usually catalyzed by enzymes present inside the body, leading to the formation of the active drug.

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Carboxylic Acids & Drug Binding

Carboxylic acid groups in drugs can interact with targets through ionic bonds or hydrogen bonding, playing a crucial role in drug-target binding and activity.

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Esterification & Carboxylic Acids

Converting a carboxylic acid into an ester can affect its ability to bind to targets, as esters lack the ability to form ionic bonds or act as hydrogen bond donors.

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Alkenes & Aromatics: Van der Waals Forces

These groups interact with flat hydrophobic regions on targets through weak van der Waals forces, contributing to the overall binding of the drug.

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Modifying OH Groups

Changing an OH group to an ether or ester can help researchers understand if the OH group was involved in hydrogen bonding and essential for drug binding. This helps predict how changes in structure impact drug activity.

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SARs

Structure-Activity Relationships; analyzing how small changes in a drug's structure affect its activity and binding to its target.

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Hydrogen Bonding in Drugs

Drugs can form hydrogen bonds with their targets, which are strong interactions that contribute to binding.

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HBD & HBA

A molecule with a hydrogen attached to an electronegative atom is called a hydrogen bond donor (HBD), and a molecule with an electronegative atom that can accept the hydrogen is called a hydrogen bond acceptor (HBA).

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Aldehyde and Ketones

Aldehydes and ketones have a polarized carbonyl group (C=O) that can interact with targets through dipole-dipole interactions or hydrogen bonding.

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Testing the Importance of a Group

Drugs often contain functional groups that contribute to binding. To determine if a functional group is important, it can be modified to see if the drug loses its activity.

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Amides and H-bonding

Converting a functional group to an amide can prevent hydrogen bonding, either as a donor or acceptor.

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Esters and Prodrugs

Esters are commonly used in drugs to mask a polar group, allowing the drug to cross cell membranes more easily. They are then hydrolyzed to the active drug in the body.

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Reducing a Carbonyl to an Alcohol

Reducing the carbonyl group of an aldehyde or ketone to an alcohol can change the geometry of the molecule and affect its dipole-dipole interactions and ability to act as a HBA.

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Testing Aromatic Groups

Changing an aromatic group to an aliphatic group can help determine if the aromatic group is essential for binding to the target.

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Van der Waals Forces

Weak interactions that occur between non-polar molecules, like alkenes and aromatics. These forces are important for binding to flat hydrophobic regions of targets.

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Target-Oriented Drug Design

A strategy for designing new drugs that focuses on improving the interaction between the drug and its target by modifying the drug's structure.

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Variation of Substituents

Modifying functional groups attached to a drug molecule to improve its binding affinity or specificity to a target.

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Extension of the Structure

Adding a new part to a drug molecule to increase its affinity or specificity to the target.

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Chain Extensions/Contractions

Changing the length of a carbon chain in a drug molecule to improve its interaction with a target.

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Ring Variations

Modifying the size or type of ring structures in a drug molecule to optimize its binding to a target.

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Ring Fusions

Combining two or more ring structures in a drug molecule to create a new molecule with enhanced binding affinity or specificity.

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Isosteres

Atoms or groups with similar chemical properties and valencies that can be substituted for each other in drug molecules without significantly altering their biological activity.

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Rigidification of the Structure

Introducing structural constraints into a drug molecule to limit its flexibility and improve its binding affinity to a target.

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SAR (Structure-Activity Relationships)

The study of how changes in the structure of a drug molecule affect its biological activity, helping identify important functional groups and design more effective drugs.

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Rigidification

Making a drug molecule more rigid by restricting its flexibility, often achieved by replacing rotatable bonds with fixed ones. Reduces side effects by locking in one conformation.

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Pharmacokinetic Properties

Factors that influence how a drug travels through the body, including absorption, distribution, metabolism, and excretion.

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Hydrophilic/Hydrophobic Character

Describes how well a drug interacts with water (hydrophilic) or fat (hydrophobic). Influences drug absorption and distribution.

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Ionization

The process of gaining or losing a charge, affecting a drug's solubility and ability to cross membranes.

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Drug Metabolism

The process by which the body chemically alters a drug, typically in the liver. This often makes the drug more water-soluble, allowing for easier excretion through the kidneys.

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Phase I Metabolism

The initial stage of drug metabolism, involving reactions like oxidation, reduction, and hydrolysis. These reactions can introduce or expose functional groups, making the drug more reactive for further modifications.

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Phase II Metabolism

The second stage of drug metabolism, involving conjugation reactions where a polar molecule is attached to the drug. This increases water solubility and promotes excretion.

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Therapeutic Window

The range of drug doses between the effective dose (benefit) and the toxic dose (adverse effects). It defines the safe and effective dosage range for a drug.

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Teratogen

A substance that can cause birth defects or developmental abnormalities in a developing fetus.

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Thalidomide

A drug that was tragically discovered to be teratogenic, causing severe birth defects in thousands of children.

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Enantiomers

Mirror-image isomers of a chiral molecule, having the same chemical formula but different spatial arrangements of atoms. They can have very different biological activities.

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Racemic Mixture

A 50/50 mixture of two enantiomers. This can be problematic if one enantiomer is active and the other is inactive or toxic.

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Metabolic Stability

A drug's ability to resist breakdown by the body's enzymes, particularly in the liver, allowing it to stay active for longer.

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Drug Metabolism: Phase I & II

The body's process of modifying drugs into more water-soluble forms for elimination. Phase I involves oxidation, reduction, or hydrolysis, while Phase II adds polar groups like glucuronide.

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Testing for Drug Metabolites

Experiments on animals and humans to determine how drugs are broken down in the body and if inactive or even toxic metabolites are formed.

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Toxicity Testing: LD50 & TD50

Measuring the lethal dose (LD50) and toxic dose (TD50) in animals to assess a drug's safety. LD50 is the dose that kills 50% of subjects.

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Thalidomide Tragedy

A drug marketed in the late 1950s with one enantiomer (R-enantiomer) effective against morning sickness, but its other enantiomer (S-enantiomer) caused severe birth defects.

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Enantiomers & Chirality

Mirror-image forms of a molecule that can have drastically different biological effects. Chirality plays a crucial role in drug development.

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Drug Manufacturing

Considerations for synthesizing a drug, including ease of synthesis, yield, number of steps, experimental procedure, purification, and economic costs.

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What is rigidification in drug design?

Introducing structural constraints to limit a drug's flexibility, often by replacing rotatable bonds with fixed ones. This improves binding affinity and reduces side effects.

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What is hydrophilic/hydrophobic character?

Describes how well a drug interacts with water (hydrophilic) or fat (hydrophobic). Influences drug absorption and distribution.

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What does target-oriented drug design involve?

Designing new drugs by improving the interaction between the drug and its target by modifying the drug's structure.

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What are some ways to modify a drug's structure in target-oriented drug design?

Modifying drug structures involves variations of substituents, extension of the structure, chain extensions/contractions, ring variations, and ring fusions.

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What is the relationship between structure and activity in drug design?

SAR (Structure-Activity Relationships) explores the correlation between a drug's structure and its efficacy, helping identify important functional groups and design better drugs.

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Pharmacokinetic Drug Design

Designing drugs with favorable properties for absorption, distribution, metabolism, and excretion in the body.

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LD50

The Lethal Dose 50, the amount of drug that kills 50% of a test population. It is a measure of acute toxicity.

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TD50

The Toxic Dose 50, the amount of drug that causes toxic effects in 50% of a test population.

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ED50

The Effective Dose 50, the amount of drug that produces a desired effect in 50% of a test population.

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Lipinski's Rule of Five

A set of rules that predict a drug's likelihood of good absorption and permeability based on its physical properties.

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What are the four parameters in Lipinski's Rule of Five?

The four parameters are: molecular weight, Log P, number of H-bond donors (OHs and NHs), and number of H-bond acceptors (Ns and Os).

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What is a lead compound?

The initial drug molecule that exhibits biological activity against a target, but may have limitations like weak activity or undesirable side effects.

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Hydrogen Bond Donors

Molecules with a hydrogen atom covalently attached to an electronegative atom like oxygen or nitrogen; they donate a proton (H+) to form a hydrogen bond.

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Hydrogen Bond Acceptors

Molecules with an electronegative atom like oxygen or nitrogen, capable of accepting a proton (H+) from another molecule.

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Molecular Weight (MW)

The sum of the atomic weights of all atoms in a molecule. For good oral absorption, it should ideally be under 500.

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Log P

A measure of a molecule's lipophilicity or its tendency to dissolve in fats. Ideal range is below 5 for good oral absorption.

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Exceptions to Lipinski's Rule

Certain drug types, like those administered non-orally, for gut conditions, or as antibiotics, might not follow the rule.

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What is a Structure-Activity Relationship (SAR)?

The connection between how a molecule is built and how it functions in the body. Scientists use SAR to improve drugs.

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The Father of Chemotherapy?

Paul Ehrlich. He pioneered the idea of using drugs to fight diseases and the concept of 'magic bullets', highly specific drugs.

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Drug Size

The molecular weight of a drug affects its ability to be absorbed and reach its target. Larger molecules may have difficulty crossing cell membranes.

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Drug Solubility

Drugs need to be soluble in both water and lipids to cross cell membranes and reach their target. Too high in either will disrupt absorption.

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What is Log P?

Log P is a measure of how hydrophobic (fat-loving) a drug is. It indicates how easily a drug can pass through lipid membranes.

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What are Isosteres?

Groups of atoms with similar chemical properties that can be substituted within a drug molecule without significantly changing its biological activity.

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Serendipity in Drug Discovery

The accidental discovery of a beneficial drug while searching for something else.

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Prepared Mind in Science

The idea that being knowledgeable and ready to observe is key to making valuable discoveries, even by chance.

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What are Structure-Activity Relationships (SARs)?

The study of how changes in a drug's structure affect its biological activity, helping to understand how different parts of a molecule contribute to its function.

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What are Hydrogen Bond Donors (HBD) and Acceptors (HBA)?

HBDs have a hydrogen atom attached to an electronegative atom (O or N) capable of donating a hydrogen bond. HBAs have an electronegative atom that can accept a hydrogen bond.

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How do you test SARs?

By systematically changing parts of a drug molecule and observing the impact on its activity, researchers can identify which functional groups are most important for binding.

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What are Prodrugs?

Inactive compounds that are converted to active drugs inside the body, often to improve their absorption, solubility, or stability.

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Oral Drug Delivery: What's the Challenge?

For a drug to be effective when taken orally, it must pass through the gut lumen, the gut wall, and into the bloodstream. This requires consideration of factors like size, solubility, and hydrogen bonding.

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Size Matters: How Big Is Too Big?

Drugs that are too large (molecular weight greater than 500) struggle to pass through cell membranes, limiting their oral bioavailability. This means they have a harder time getting absorbed into the bloodstream.

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Solubility: Finding the Right Balance

Drugs must be soluble in both water and lipids (fats) to navigate the aqueous environment of the gut and the lipid membranes of cells. Too much solubility in either is not ideal.

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Log P: Measuring Solubility Preferences

Log P is a measure of a drug's partitioning between octanol (a lipid-like solvent) and water. A higher log P value indicates greater lipid solubility.

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Hydrogen Bonding: The Glue That Holds It Together

Hydrogen bonds are crucial for drug-target interactions. They are formed between electronegative atoms like oxygen (O) or nitrogen (N) and hydrogen (H) atoms.

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Too Many H-Bonds? A Sticky Situation

If a drug has too many hydrogen bonds, it can stick too tightly to itself or other molecules, making it difficult to cross cell membranes.

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What Does Log P Tell Us? A Drug's Preference

A high Log P value suggests a drug is very hydrophobic (it prefers fats). Such drugs tend to get trapped in cell membranes and struggle to reach their targets.

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Hydrophilic/Hydrophobic: A Drug's Personality

A drug's hydrophilic (water-loving) or hydrophobic (fat-loving) character influences how it moves through the body. Hydrophilic drugs are better at moving in the blood.

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Molecular Weight

The sum of the atomic weights of all atoms in a molecule. In Lipinski's Rule, a molecular weight over 500 is less likely to be well absorbed.

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H-bond Donors

Atoms in a molecule that can donate a hydrogen atom to form a hydrogen bond. Lipinski's Rule suggests more than 5 donors are unfavorable for absorption.

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H-bond Acceptors

Atoms in a molecule that can accept a hydrogen atom to form a hydrogen bond. Lipinski's Rule suggests over 10 acceptors are unfavorable for absorption.

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Paul Ehrlich

A pioneer in chemotherapy who coined the term 'magic bullet' and developed the first effective treatment for syphilis. He was also a key figure in the development of SAR.

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Lead Optimisation

The process of improving a drug's efficacy, such as its stability and how well it's absorbed by the body.

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How do you test an aromatic group's effect on drug activity?

You can change an aromatic group to an aliphatic group to see if the drug loses activity. This tells you if the aromatic group is essential for binding.

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What are some ways to optimize a lead compound?

There are several ways to optimize a lead compound, such as: varying substituents, extending the structure, chain extensions/contractions, ring variations, ring fusions, and rigidification.

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Analogues

Molecules that are structurally similar to a known active compound.

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Aromatic Group

A cyclic group of atoms with alternating single and double bonds, contributing to a molecule's lipophilicity and potential for van der Waals interactions.

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Serendipity

Finding something valuable by chance, especially while looking for something else.

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Prepared Mind

The ability to recognize and understand opportunities due to knowledge and experience.

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Oral Activity

A drug's ability to be absorbed into the bloodstream after being taken by mouth.

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Oral Drug Delivery

The process of a drug being administered by mouth and passing through the gastrointestinal tract to reach the bloodstream.

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Why is Size Important?

Molecules larger than 500 g/mol have difficulty passing through cell membranes.

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What is Solubility?

The ability of a drug to dissolve in a solvent (like water or lipids).

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What is a Good Log P?

A good log P value for oral bioavailability is generally between 0 and 5, meaning the drug has a balance of water and lipid solubility.

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How Many Hydrogen Bonds?

Drugs with too many hydrogen bonds (> 10) can be too strongly attracted to themselves, making it difficult to reach their target.

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Amines & Targets

Amines interact via ionic bonds due to their positive charge and hydrogen bonding, acting as both donors and acceptors.

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Carbonyl Groups

Carbonyl groups are hydrogen bond acceptors (HBAs), attracting hydrogen atoms from other molecules.

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Why Esters in Prodrugs?

Esters help drugs cross cell membranes easier, delivering them to the target.

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Study Notes

Drug Structure, Function & Properties

  • Drug properties are determined by functional groups and stereochemical features.
  • Drugs interact with targets (active sites) to trigger biological responses.
  • Drug administration methods include swallowing, injection, inhalation and application.
  • Drugs travel to their site of action to interact with the target, initiating a biological response.

Learning Objectives

  • Identify functional groups in drug molecules and other features like stereochemical properties in the drug structure.
  • Relate the functional groups and other features to drug properties.
  • Recognize and describe binding forces between drug molecules and their targets/active sites.

Aims for Lecture 1

  • Understand drug interaction mechanisms and locations.
  • Appreciate protein structure principles.
  • Know the forces impacting protein structure.

So far in Semester 1 and 2 (PH1015)

  • Covered general structural properties of molecules, bonding, hybridisation, aliphatic functional groups, stereochemistry, and heterocyclic compounds.
  • Students should remember drugs are molecules with specific effects on the body.

Predicting Drug Properties

  • Recognizing functional groups predicts chemical properties like solubility, reactivity, stability, ionization characteristics, and acid/base properties.
  • Recognizing functional groups enables prediction of absorption and potential activity within the body.

How Do Drugs Work?

  • Drugs are administered via various routes (swallowed, injected, inhaled, applied, inserted).
  • Drugs travel to their target site where they interact with a target and trigger a biological response.

Drug Absorption, Distribution, Metabolism & Excretion

  • Drugs undergo absorption, distribution, metabolism, and excretion processes.
  • Drugs are absorbed through various routes, including transdermal, subcutaneous, rectal, buccal, sublingual, intravenous, and oral routes.
  • Drug targets interact with receptors, undergo diffusion and/or absorption in tissues before reaching the bloodstream.
  • The blood carries the drug to its target, and it undergoes metabolism in the liver and excretion through the kidneys.

Transport Mechanisms

  • Drug molecules typically cross cell membranes except through intravenous injection.
  • Passive diffusion, facilitated diffusion, active transport, and pinocytosis are basic transport mechanisms in this process.

Where Do Drugs Work?

  • Drugs act on cells.
  • Drug targets can be lipids, carbohydrates, or proteins, with the majority being proteins and nucleic acids, often located in cell membranes.
  • Often, only a specific area of a protein will interact with a drug molecule.

Protein Structure

  • Primary structure: Sequence of amino acids linked by peptide bonds.
  • Secondary structure: Alpha helix (coiling held together by hydrogen bonds), beta-pleated sheets (layering held by hydrogen bonds).
  • Tertiary structure: Overall 3D structure dependent on interactions (covalent, ionic, hydrogen bonds, Van der Waals).

Protein 3 Structure Forces

  • Covalent: Strongest (e.g., disulfide bonds).
  • Ionic: Strong between groups with opposite charges.
  • Hydrogen: Between electronegative atoms and protons.
  • Van der Waals: Weakest, hydrophobic interactions.

Forces Producing Tertiary Structure

  • Intramolecular forces (e.g. hydrogen bonding and ionic interactions) shape the tertiary structure of proteins.

Drug Binding Sites

  • Drugs bind to specific regions (binding sites) within larger structures like proteins, enzymes, nucleic acids, lipids, and carbohydrates.

Binding Interactions

  • Functional group structure determines a molecule's properties, including intermolecular bonding capability.
  • Intermolecular forces are essential for drug-target combinations.

Controlling Protein 3 Structure

  • The forces (ionic, hydrogen, van der Waals , dipole-dipole, and covalent bonding) controlling protein 3D structure are also seen in the interactions between drugs and their targets.

Summary

  • Many drugs cross cell membranes.
  • Lipids, carbohydrates, proteins, and nucleic acids can be drug targets, with proteins and nucleic acids being most common.
  • Protein tertiary structure depends on intramolecular bonding forces.
  • These same forces are responsible for drug-target interactions.

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Related Documents

Drug Structure, Function & Properties PDF
Drug Structure, Function & Properties Lecture 2 PDF
Drug Structure, Function & Properties Lecture 3 PDF
Drug Design & Drug-Target Interactions PDF
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