Drugs from Natural Sources

3 criteria to assess importance of natural products in modern world

1. Rate of introduction of new chemical entities of wide structural diversity (including serving as template for semisynthetic drugs)

2. The number of diseases treated/prevented by these substances.

3. Their frequency of use in the treatment of disease

Digoxin source

Foxglove

Known previously as gypsy weed

Morphine contribution to science

understand opiate receptor subtypes and discovery of endogenous ligands which act on these receptors (e.g. Endorphins produced after exercise)

Epibatidine use

200 times more potent than morphine - too potent for human use

Different pharmacophore (nicotinic not opioid receptor)

Epibatidine drug

ABT-594 less potent version

Tebanicline dropped phase 2 clinical trial

From skeleton: Apomorphine (2004): short acting on dopamine D1, D2 receptors, now used in treatment of early Parkinson's disease

Aspirin source

Semi synthesised from willow bark

Penicillin contribution to science

synthesis of countless analogues of penicillin and cephalosporin antibodies

Enabled understanding of infectious disease - MRSA now developed (methicillin-resistant staphylococcus aureus) a type of antibiotic-resistant bacteria.

Penicillin source

Slime mould

Quinine drug

Chloroquinine recently developed (chloroquine resistant parasites now appearing)

Artemisinin drug

Artemether: antimalarial agent (derivative of artemisinin)

Only important group was peroxide - variable analogues created

Atropine use

Competitive cholinergic antagonist (anticholinergic drug) that acts on muscarinic receptors

Atropine drugs

Applied topically (mydriatic to dilate pupils) : cycloplegic which temporarily paralyzes the accommodation reflex

Basis for tiotropium bromide, treats bronchospasm associated with COPD

Vincritine drug

Vinblastine is anti-mitotic

Used to treat some cancers (leukaemia, Hodgkin's lymphoma, breast and testicular cancer etc)

binds tubulin which inhibits assembly of microtubules

M phase of cell cycle specific

chemical analogue of vincristine

Vinca alkaloid

Toxic effects: bone marrow suppression, GI toxicity, vesicant (blister forming) activity and extravasation injury (deep ulcers)

Taxol drug

Paclitaxel: chemotherapy drug used in breast, ovarian and lung cancer treatment

ginseng use

presence of ginsenides

Traditional Chinese Medicine Panax ginseng

promotes Yang energy, improves circulation, increases blood supply, revitalizes and aids recovery from weakness after illness and stimulates the body.

Ginseng drug

PROTOPANAXADIOL

Derivative of triterpene glycone of several saponins from Ginseng

apopototic effects on cancer cells (signaling pathways) and cytotoxic against multidrug resistant tumours

Ginkgo contains...

Diterpenes which are completely oxidised.

Ginkgo use

Extract of the Ginkgo leaves contains flavonoid glycosides and

terpenoids and has used pharmaceutically

used as memory and concentration enhancer, and anti-vertigo

agent

dicoumarol

interferes with the effects of vitamin K in blood coagulation, blood loses ability to clot, thus minor injuries can lead to severe internal bleeding

dicoumarol drug

Synthetic dicoumarol

oral blood anticoagulant in treatment of thrombosis as well as salts of warfarin and acenocoumarol (synthetic developments from the natural product)

Valerian use

herb or dietary supplement prepared from roots (maceration, trituration, dehydration processes)

sedation and anxiolytic effect

Iridoids present: strong antipressant activity

Producer of ciguatoxin in tropical regions

Dinoflagellate Gambierdiscus toxicus (Algae)