Lecture -10: The Chemistry of Life PDF

UGEB2380 The Chemistry of Life Academic Year 2024-25 Dr. Sam CK HAU (Department of Chemistry) Medicines and Drugs Medicines and Drugs Defined as a chemical substance that affects the functioning of living things Used to treat, diagnose, and prevent diseases People use drugs for many...

UGEB2380 The Chemistry of Life Academic Year 2024-25 Dr. Sam CK HAU (Department of Chemistry) Medicines and Drugs Medicines and Drugs Defined as a chemical substance that affects the functioning of living things Used to treat, diagnose, and prevent diseases People use drugs for many reasons i. To relieve pain ii. To fight infections iii. To stay awake iv. To get to sleep v. To calm anxiety vi. To prevent conception vii. To treat various conditions from arthritis to heart disease to pneumonia to cancer 3 Drug Development In the US, more than 4 billions prescriptions are written each year and producing annual sales in excess of $320 billions Begins with identifying drug candidates - chemical compounds show biological activity being selected & identified > - effect in our body chemicals Through a variety of means body cycle > - how drug function in 1. Rational drug design - a process requires identifying a biological molecules that involved in causing a disease, then design molecules to interact that target 2. High-throughput screening - applying robotics to screen thousands of compounds > look for any interference (eg interrupt - enzymes etc) 3. Serendipity or chance => found accidentally 4. Chemical modification of existing drugs in order to improve their efficacy and/or reduce side effects & ar have a drug outside the market 4  Drug Development Literally thousands of compounds may be screened and tested before receives marketing approval by the authority like the FDA - (inUS) Time consuming and take 15 years or more to get approval Expensive, particularly for the clinical trials, which test drug candidates in human subjects and to determine whether the drug candidate ↓ provides better clinical outcomes than a placebo (an inert substance used as a scientific control in tests of an actual ↳ medication) fro pool all psychological effect may be larger pool significant to 5 Drug Development New introduced drugs are sold under patent protection Prevent other companies from making and selling the same medicine while the patent is in force Once the patent expires, other companies may sell a generic form of the drug (drugs that are chemically equivalent to patented drugs) and less expensive with the same purity, safety, strength and performance characteristics 6 Nonprescription Pain Relievers Late 19th century, semi- synthetic drugs - made by chemical modification of a natural product Natural product - a chemical compound produced by a living organism EAspirin is an example With more than 2400 years history Hippocrates (ancient Greece) - a physician Sick people ease their pain and lower their fever by chewing willow leaves ( *p 7  Aspirin Until 1835, it is isolated from willow leaves as the active ingredient Effective analgesic (pain o reliever); antipyretic (fever reducer) and anti- inflammatory But causes considerable · : don't use stomach distress and aspirin as bleeding pain kil er r more Introduced by Bayer in 1893 O C OH O C O CH3 8  (NSAIDs) Non-steroidal Anti-inflammatory Drugs Aspirin is one example; others including Ibuprofen (Advil®, Motrin®), Naproxen (Aleve®), and Ketoprofen (Orudis®) O OH O OH CH3 O C O C H 3C C OH CH3 C H 2C CH3 CH3 H3CO Ibuprofen Naproxen Ketoprofen Act to relieve pain and reduce inflammation by inhibiting the production of prostaglandins, hormone-like lipids that are involved in sending pain messages to the brain Inflammation is caused by an overproduction of prostaglandin derivatives Not cure the problem causing the pain but “kill the messenger” 9 NSAIDs Prostaglandins affect the blood platelets, the kidneys and the stomach lining ⟶ side effects by NSAIDs to cause excessive bleeding and stomach pains NSAIDs exhibits the anticoagulant effect (inhibition of the clotting of blood); small daily doses can lower the risk of heart attack and stroke minimize blood clotting in blood vessels - >.. now use treat Not suitable for people aspirin to heart disease facing surgery, childbirth, or but not some other hazard involving as pain killer the possible loss of blood 10  feel Narcotics all > - don't anything at Pain is too great to be relieved by normal drugs, stronger prescription drugs are available Produce narcosis (stupor or general anaesthesia) and analgesia (relief of pain) effects but are also found to be addictive Used to be products of (k) Opium, from the dried, & resinous juice of the unripe seeds → Morphine (o) 11 Morphine Morphine was first isolated in 1805 Was widely used during the wars for relief of pain of soldiers due to battle wounds One major side effect of morphine use is Constipation and Addiction Still used by prescription for the relief of severe pain; also induces lethargy, drowsiness, confusion, euphoria, chronic constipation, and depression of the respiratory system (breathe very slowly 12 Morphine Derivatives * Codeine is similar↑to morphine -moditythe of morphine in action, less potent, less tendency to induce sleep, and less addictive Morphine For cough suppression, codeine is given in liquid preparations Conversion of both -OH groups when you take to acetate ester groups > it in - => produce Heroin - induce you Codeine -> 'her" become addiction more quickly and was harder to cure Addiction probably has three components: psychological dependence (uncontrollable desire), physical dependence (withdrawal symptoms) and Heroin tolerance (increasing dosages) Drugs and Infectious Diseases 100 years ago, infectious diseases were the main cause of death Nowadays, this category drops to the bottom of the list The situation is brought under control through the use of antibacterial drugs The first antibacterial drugs were sulfa drugs, which was extensively used during WWII to prevent wound infections 14 Antibiotics Substances originally derived from certain moulds and fungi that kill other microbes Penicillin was first discovered in 1928 but was applied until 1941 Alexander Fleming - during his Smuda investigation of infectious bacterium and one of his cultures became contaminated with a blue mould and he noted that bacterial colonies had been destroyed in the vicinity of the mould Fleming made crude extracts of the active substance, which was known as Penicillin and later be further purified and improved by Howard Florey and Ernst Boris Chain Penicillin of chemical compounds Not a single substance but a mixture > - group of related compounds H H Chemists produce penicillins N S CH3 with variable effectiveness O by designing molecules with N CH3 O different structures OH O Some can be taken orally, Penicillin G others must be injected - for high dosage NH2 Penicillins account for about H N H half of all antimicrobial HO S CH3 prescriptions O N CH3 Amoxicillin has a broad O OH spectrum of activity against O many types of Amoxicillin microorganisms 16 How it works … porous = no cell wall to Penicillin works by inhibiting ↓ protect bacteria enzymes that the bacteria use to make their cell walls The bacterial cell walls are made up of mucoproteins, polymers in which amino sugars are combined with protein molecules Penicillin prevents cross- linking between these large molecules and generate holes in the cell walls, then the bacteria swell and rupture Higher animals’ cells have only external membranes, are not affected by penicillin 17 Antibiotics Worked miracles in our time but are not without problems Disease organisms develop strains resistant to them → one strain can spread antibiotic resistance to another by sharing genes, and the emergence of more and more resistant strains of bacteria A serious threat to world health Tuberculosis had been completely wiped out in developed countries but a drug-resistant strain has become rampant in Russia and among AIDS patients 18 Antibiotics vs. Drug Resistance pump antibiotic chemical out find other chemicals to consume antibiotic antibiotic cann of recognize them  bacteria are alive Viruses > -dead > waiting - to find a host & replicate themselves Viral diseases cannot be cured by antibiotics Viral infections, from colds and influenza to herpes and Acquired Immune Deficiency Syndrome (AIDS) Why won’t doctors give an antibiotic for a cold? Colds are the result of many different viruses the -recognize Be prevented by virus rehearse = knows what vaccination: Influenza body : when to do vaccines are quite effective true virus come against common recurrent strains of flu viruses 20 DNA Viruses and RNA Viruses Composed of nucleic acids cambeen - or DNA and proteins External coat that shows a repetitive pattern of protein molecules, some include a lipid membranes or sugar- protein combination (glycoproteins) DNA Virus moves to the location in a host cell where the DNA is replicated and directs the host cell to product viral proteins; the viral proteins and viral DNA assemble into new viruses and released to transcribe to DNA need RNA first 21 DNA Viruses and RNA Viruses RNA viruses penetrate to where the RNA strands of a host cell are replicated and induces the synthesis of viral proteins Some RNA viruses called retroviruses, synthesis DNA in the host cell; reverse the transcription DNA into RNA Human Immunodeficiency Virus (HIV) invades and eventually destroys T cells (white blood cells) that help protect the body from infections; once be destroyed, the victim often succumbs to pneumonia or other infections 22 Antiviral Drugs if virus level is => may not be effective VERY high A variety of drugs that are effective against some viruses but not providing cures CH3 H3C CH O HN HN N N N N N HOH2C H3CO2SHN N O N O H Didanosine (ddI) Delavirdine a nucleoside analog or Non-nucleoside reverse nucleoside reverse transcriptase transcriptase inhibitor (NNRTI) inhibitor (NRTI) N O O COOCH2CH3 H N N N H OH HN O O NH2 NH2 O O NHC(CH3)3 Saquinavir Tamiflu® Protease inhibitor Prevent influenza in early stages 23 Antiretroviral Drugs Prevent the reproduction of retroviruses such as HIV and are used against AIDS Three important kinds x sth looking like nucleoside ⑨ 1. Nucleoside analogs or nucleoside reverse transcriptase inhibitors (NRTIs): substitution of an analog for a nucleoside in viral DNA cripples the retrovirus, slowing down its replication 24 Antiretroviral Drugs Prevent the reproduction of retroviruses such as HIV and are used against AIDS Three important kinds targeeme of & transcription ⑧ 2. Non-nucleoside reverse transcriptase inhibitors (NNRTIs): stop the reverse transcriptase from enzyme make more of the ( working properly to function cannot well retrovirus 25 Antiretroviral Drugs Prevent the reproduction of retroviruses such as HIV and are used against AIDS targetting Three important kinds- > protein ⑧ 3. Protease inhibitors block the enzyme I protease so that new copies of the retrovirus can’t infect new cells stop nutrients 26 Drugs for the Heart Diseases of the cardiovascular system - responsible for more than one-fifth of deaths worldwide Major diseases of the heart and blood vessels include: ➡ Ischemic “lacking oxygen” coronary artery disease ➡ Heart arrhythmias (abnormal heartbeat) ➡ Hypertension (high blood pressure) ➡ Congestive heart failure 27  cholesterol. Drugs for the Heart - high density" can decrease lipid deposit cholester Atherosclerosis (buildup of e fatty deposits in the lining of the arteries) - the primary cause of coronary artery disease, in turn causes myocardial infraction (heart attack) Most drug treatments for the heart aim to increase its supply of blood and oxygen → normalise its rhythm → lower blood pressure → prevent accumulation of lipid plaque deposits in vessels 28 Lowering Blood Pressure Blood pressure - pressure in millimetres of mercury (mmHg) Hypertension or high blood pressure - above 140/90 Normal blood pressure is below 120/80 Four major categories of drugs => to tackle blood pressure problems 1. Diuretics 2. Beta blockers 3. Calcium channel blockers 4. Angiotensin-converting enzyme (ACE) inhibitors 29 Lowering Blood Pressure Diuretics - the oldest, simplest and cheapest of the blood-pressure-lowering water contentd drugs → cause the kidneys pressured to excrete more water and ↑ thus lower the blood volume Beta blockers → slow the heart rate and reduce the force of the heartbeat Calcium channel blockers vessels - powerful vasodilators → can be more inducing muscles around X elastic the blood vessels to relax ACE inhibitors - inhibit the action of an enzyme that causes blood vessels to contract = dilate blood vessels 30 Drugs and the Mind Psychotropic Drug - affects the human mind No clear distinction between drugs affecting the mind and those affecting the body; most probably affect both mind and body Can be divided into three classes ➡ Stimulant Drug ➡ Depressant Drug ➡ Hallucinogenic Drug 31 Stimulant Drugs Three plant alkaloids (a class of plant compounds that give a bitter taste and contain the basic amino group) direct from Cocaine hydrochloride - membrane of readily absorbed through the ↑ nose to brain mucous membrane of the nose (preventing the re-uptake of dopamine and leaving high levels of dopamine to stimulate the pleasure centres of the brain) - increase stamina and reduce fatigue Caffeine - mild addictive and less hazards Nicotine - powerfully addictive and lethal dose for a human is estimated to be about 50 mg 32 Stimulant Drugs Such as cocaine or an amphetamine - increase NH2 NH2 alertness, speeds mental processes and generally elevates the mood 𝛽-Phenylethylamine Amphetamine Act by increasing levels of norepinephrine, serotonin, and O O dopamine in the brain H H N N Either methylphenidate (Ritalin®) or a mixture of amphetamines - treat attention deficit hyperactivity disorder Methamphetamine Methylphenidate (ADHD) in children OH Long-term effects of NH2 methamphetamine use include severe mental problems, loss of memory, and serious dental Phenylpropanolamine problems 33 Depressant Drugs Such as alcohol, almost any aesthetic, an opiate, a barbiturate, or any of certain tranquillisers, reduces the level of consciousness and the intensity of reactions to environmental stimuli Ethanol slows down both physical and mental activities Moderately use of alcohol - live longer than nondrinkers; Heavier drinking - cause many health problems Alcoholic beverages are generally high in calories; drinking too much alcohol causes fat to be deposited, mainly in the abdomen 34 Depressant Drugs need doctor > prescription Barbiturates - induce sleep and widely prescribed as sleeping pills but be replaced by drugs like benzodiazepines (less potential for abuse and less lethal) Especially dangerous when ⑭ ingested along with ethanol - produces a perhaps ten times greater effect than the sum of the two (synergistic effect) 1 + 12 Strongly addictive with side effects like hangovers, drowsiness, dizziness and headaches 35 Hallucinogenic Drugs Consciousness-altering substances that induce changes in sensory perception; qualitatively altering the way users perceive things Natural: psilocybin mushrooms ( ); Synthetic: MDMA “Ecstasy”, Dimethyltryptamine (DMT) and PCP and ketamine; Semisynthetic: Lysergic acid dethylamide (LSD) and Mescaline I will keep on their shaking head 36 Hallucinogenic Drugs LSD is a powerful hallucinogen - accidentally discovered by a Swiss Chemists Albert Hofmann (1906-2008) in 1943 through unintentionally ingestion of 250 mg. The usual does for a human is about 10-100 μg Create a feeling of lack of self-control Exact mechanism is still unknown but suspect to act on dopamine receptors and excite by increasing the release of glutamate (a neurotransmitter) 37