Pharmacology and Drug Discovery Quiz

Study Notes

Lecture 1 topics: introduction to phytotherapy and natural product chemistry, types of natural products, classifications of natural products (primary and secondary metabolites), drug discovery (rational drug design, combinatorial chemistry, natural products), primary metabolites (sugars, glycolysis, phosphoenolpyruvate pathways, fats, amino acids, peptides, proteins), secondary metabolites (classification, importance as therapeutic agents)
Natural products are chemical compounds produced by living organisms
Phytochemistry is the study of naturally occurring compounds found in plants
Natural products are used in various applications including as food, perfumes, coloring agents and therapeutic agents.
Drug discovery relies on continuous processes, partly driven by the emergence of new diseases and drug resistance
Often drugs in the past were discovered due to observation of natural products.

Natural products are old fashioned but are compatible with modern technologies, commonly used in drug discovery.
The difficulties of isolating and purifying natural products are overestimated.
Classification of natural products is important to understand drug discovery
Natural products have structural diversity, thus suitable for drug targets that would otherwise be difficult to synthesis.
Natural products provide a wide range of pharmacophores

Secondary metabolites are not essential for growth
The adaptation of organisms to specific environments or functions are due to these metabolites
They are more important than primary metabolites as therapeutic agents.
Examples are Glycosides, Complex polysaccharides, Aminoglycosides, antibiotics, Phenyl propanoids, Alkaloids, Peptides, Penicillins, cephalosporins, Erythromycins, Tetracyclins, anthraquinones, Terpenoids, steroids
These metabolites are derived from primary metabolites through secondary metabolic pathways.

Natural products are classified as primary metabolites and secondary metabolites, depending on whether they are needed for the survival and growth of the organism.

Drug discovery and development is a continuous process because of the emergence of new diseases and drug resistance.
Rational drug design involves tailoring a drug to fit its intended target.
Combinatorial chemistry prepares a huge number of compounds for testing against a target.
Natural products are utilized as a source of drug leads.

The building blocks for natural products are derived from glucose through Glycolysis and Pentose Phosphate Pathways
Important molecules involved: amino acids, lipids, and photosynthesised sugars

Photosynthesis and aerobic respiration are essential biological processes, providing the building blocks for many natural products
The chemistry of natural products involves various chemical reactions.
Various reactions play a role in the formation of these products including; oxidation and reduction reactions, ester formation, imine formation, and transamination

This pathway, crucial for the synthesis of diverse lipid and aromatic compounds, is central to natural product formation.
Aldol and Claisen Reactions are key reactions here

Macrolides are a large group of compounds characterized by a macrocyclic lactone ring.
These molecules are commonly found in nature and exhibit antibiotic activities.

Erythromycins were first isolated from Streptomyces erythreus ( now known as Saccharopolyspora erythrea).
The commercial erythromycin is a mixture of Erythromycin A, B, and C.
These molecules are naturally produced, and are important antibiotics
These molecules are structurally different and thus have a different set of activities.

Amphotericin B and Nystatin are extracted from bacteria and fungi, respectively.
The mechanism of action involves binding to ergosterol, a sterol found in fungal cell membranes.
These drugs are primarily used for treating fungal infections.

Ascomycin is obtained from the fermentation of Streptomyces hygroscopicus, while tacrolimus is extracted from Streptomyces tsukubaensis.
Both molecules are immunosuppressants utilized in organ transplant surgeries.
They have strong immunosuppressive properties and are used to prevent organ rejection post surgery.

Sirolimus, also known as rapamycin, is extracted from Streptomyces hygroscopicus
It's an immunosupressant, used in organ transplant surgeries
It inhibits T-cell activation, leading to immunosuppression.

Rifamycins are used as a broad spectrum of antibiotics
They are derived from cultures Streptomyces and are also a class of antineoplastic agents.
Rifampicin is notable for its anti-bacterial activity.
Rifapentine demonstrates activity against Mycobacterium tuberculosis and related microorganisms.

Tetracyclines are broad-spectrum antibiotics produced by species of Streptomyces.
The tetracycline structure is amphoteric.

Aromatic polyketides are commonly encountered as the result of a variety of chemical reactions.
This is a class of naturally occurring products that often have remarkable pharmacological properties and specific application in medicine.

Phenylpropanoids are a group of aromatic compounds that are frequently encountered in natural products.
Some are used for pain relief; others have a broader application as antioxidants.
Various compounds are notable for their properties.