Natural product Discovery lead

In addition to this historical success in drug discovery, natural products are likely to continue as sources of new commercially viable drug leads. The chemical novelty associated with natural products is higher than that of any other source 40% of the chemical scaffolds in a published database of natural products (Dictionary of Natural Chemistry). This is particularly important when searching for lead molecules against newly discovered targets. Despite commonly held assumptions, natural products can be a more economical source of chemical diversity than the synthesis of equivalent diverse chemicals. 

Commercial evidence also supports the case for natural products. Of the 20 best-selling non-protein drugs in 1999, nine were either derived from or developed as the result of leads generated by natural products (e.g., simvastatin, lovastatin, ciprofloxacin, clarithromycin and cyclosprin) with combined annual sales of greater than US 16 billion. Newer developments based on natural products include the antimalarial drug artemisinin, and the anticancer agents taxol, docetaxel and camptothecin. In addition to the historical success in drug discovery, natural products are likely to continue to be sources of new commercially viable... 

Examination of the various classified listings of herbicides provides iasight iato the processes and approaches that lead to the discovery of new pesticides. The four principal development approaches are random screening, imitative chemistry, testing natural products, and biorational development. 

Medicinal chemistry has frequently drawn inspiration and important new leads from the examination of natural products, and this was proven to be the case once more. In 1992, researchers at Merck and Glaxo announced, almost simultaneously, the independent discovery of the same new class of natural products from two different fungi. As a consequence, the same family of natural products has two names - the zaragozic acids (Merck)4 or the squalestatins (Glaxo).5 A typical member of the family, zaragozic acid A (squa-lestatin SI) (1) was shown to have a tremendous affinity for squalene synthase (K, = 79 pM for rat microsomal squalene synthase) and could even lower serum cholesterol levels in vivo in a population of marmosets.6... 

With the discovery and structure elucidation of bonellin (1) and factor I (2), both naturally occurring chlorins. the systematic investigation of total synthetic approaches leading to these natural products and other chlorins was induced.4... 

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