Natural Products as Leads for New Pharmaceuticals

Abstract

A review of the use of natural products as starting points in the search for new pharmaceuticals, covering the broad areas of “Drugs affecting the centeral nervous system, ” “Neuromuscular blocking drugs,” “Anticancer drugs,” “Marine sources,” “Antibiotics,” “Cardiovascular drugs,” “Antiasthma drugs,” and “Antiparasitic drugs.” The review covers more than 100 years of development, from “old” drugs, such as morphine and quinine, to very recent discoveries, such as conotoxin and galantamine, and includes a discussion of the attributes of natural products as leads in the drug discovery process. Between 1990 and 2000, a total of 41 drugs derived from natural products were launched on the market by major pharmaceutical companies. In the chosen examples, the process of drug development is traced from the discovery of the activity of the natural compound, through chemical modification and biological evaluation, to either success or failure as a clinical product, highlighting the very different pathways to innovation that occur in each product.

QSAR of Antimalarial Cyclic Peroxy Ketals II: Exploration of Pharmacophoric Site Using AM1 Calculations

“…Plasmodium falciparum histidine rich protein 2 (Pf HRP2), a 30 kDa protein composed of several His-His-Ala-His-His-Ala-AlaAsp repeats and present in parasite food vacuole, binds with haem and plays a key role in the formation of haemozoin [16,17]. Artemisinin has a very high affinity for haemozoin present within the parasites leading to highly selective accumulation of the drug in the parasites [18,19]. Intraparasitic haem-iron catalyzes the cleavage of endoperoxide bridge and generation of carbon-centered free radicals which subsequently alkylate essential malarial proteins [2,[11][12][13][20][21][22].…”

A comprehensive review on the phytochemical and pharmacological aspects of Podophyllum hexandrum: a high value medicinal plant

“…Podophyllotoxin binds at the clochicine site of tubulin, inhibiting microtubule assembly and arrests the cell cycle in metaphase [45]. Podophyllotoxin also appears to attach to cell proteins and act by increasing the incorporation of amino acids into proteins, inhibition of purine synthesis and inhibition of purine incorporation into RNA.…”

Aspects of Chirality in Natural Products Drug Discovery

“…73 Looking at the marketed drugs derived from the natural product pool (this could be the natural product itself, a semi-synthetic derivative thereof, or a derivative generated by total synthesis), the average number of chiral centers is higher than the average of the drug pool. About 40 drugs derived from natural products were launched between 1990 and 2000, and most of them were chiral containing eight chiral centers in average [19].…”