Lecture 5.3 (natural products) Flashcards
What are natural products?
Natural products (NPs) are typically produced by organisms in response to external stimuli such as nutritional changes, infection and competition
Name some sources of natural products.
terrestrial plants, animals (vertebrates and invertebrates), minerals, microorganisms, and marine organisms
Why develop natural products into drugs?
sheer chemical diversity
In pre-industrialized society and in agrarian societies, what were plant derived NPs used for?
ranging from infections to emphysema (a progressive lung disease)
- morphine in 1806
- quinine in 1823
- atrophine in 1833
What led to an area expansion from plants to microorganism in the field of using NP as therapies for diseases?
discovery of penicillin in 1928
By 1964, NP-focused drug discovery has resulted in:
- antibacterial agents
- anti fungal drugs
- antitumor agents
What are the challenges in NP screening?
- NP are presented as mixtures in extracts or available in small quantities –> labour-intensive and time consuming purification procedures for isolation
- longer time to progress from hit to its structure –> limited speed when compared with synthetic chemical for which the structure is known
- NPs are structurally complex. –> difficult structural elucidation
- lack of skill set required to building and maintaining NP library
- difficulties in access and supply
- concerns about IP rights
Why are NPs considered ‘ugly ducklings’ by medicinal chemists?
NPs have undesirable features such as large size, too many functional groups that need to be protected (e.g. multiple hydroxyl moieties) and the presence of chiral centers
Why have NP-based drug screening come back to spotlight?
- combinatorial libraries lacked the “complexity” and “diversity” offered by nature
- Features associated with natural products are crucial for the desired bioactivities
What features associated with NPs are sometimes crucial for desired bioactivities?
multiple chiral centers, heterocyclic substituents, and polycyclic structures
Natural products chemicals are often tested as crude extracts first, followed by activity-guided isolation and identification of active compounds.
True or false.
True
Name some drugs in the market today that were discovered from natural sources.
- aspirin
- penicillin
- taxol
The complex structural type and diversity of natural products chemicals are sometimes not achievable by synthetic methods.
True or false
True
Currently how is taxol produced?
plant cell fermentation (PCF) technology
What NP-based Drug Screening Can Offer?
- infinite source of chemical diversity
- The scaffolds/ring systems found in NP that are not achievable by synthesis
- NPs as templates for combinatorial chemistry –> focused libraries of natural product analogues –> enhance drug-like properties
- discovery and better understanding of targets and pathways
- NPs can sometimes go straight from “hit” to drug unlike synthetic drugs
NPs can sometimes go straight from “hit” to drug
True or false
True
Name some NP drugs that reached the market without any chemical modifications.
- cholesterol-lowering agent lovastatin
- antibacterial agents penicillin G
- antifungal agents amphotericin B
What are some major therapeutic areas of NPs and related drugs?
antibacterial, anticancer, anticoagulant, antiparasitic, and immunosuppression
Name some well-known NP drugs
◼ Lovastatin (anticholesterolemic)
◼ Cyclosporin A, Tacrolimus (immunosuppressive)
◼ Paclitaxel and Doxorubicin (antitumor agents)
◼ Erythromycin (antibiotic)
What are some examples of alternate medicine?
chiropractic, herbal therapy, traditional Chinese medicine (TCM), meditation, yoga, acupuncture, and diet- based therapies
What is TCM?
traditional Chinese medicine
