Natural-product-based drug development

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Fig. 1. Flowchart for drug discovery, development and approval of a natural product-based drug.

Natural Product-Based Drugs in Clinical Developments... 

Natural products continue to play a dominant role in the discovery of leads for the development of drugs to treat human diseases. Such chemical agents have traditionally also played a major role in drug discovery and still constitute a prolific source of novel chemotypes or pharmacophores for medicinal chemistry. Natural product-based scaffolds find key importance in drug discovery as well as in optimizing chemical diversity... 

Scheme 2. The indole core structure is present in natural products and drugs, like for example Indomethacine and can therefore be considered as a privileged structure. A resin-capture-release strategy to synthesize an indole based compound library has been developed by Waldmann and co-workers.

Hudson, J. Towers, G. H. N. Phytomedidnes as antivirals. Drugs Future, 1999,24 295-320. Yang, S. S. Cragg, G. M. Newman, D. J. Bader, J. P. Natural product-based anti-HIV drug discovery and development facilitated by the NCI developmental therapeutics program. J. Nat. Prod., 2001, 64 265 277. 

A new approach termed Biology Oriented Synthesis (BIOS) has been developed recently by Waldmann et alf This approach is based on the structural similarity between small bioactive molecules on the one side and their receptors, that is proteins, on the other side as well as on the complementarity of both. BIOS employs compound classes from biologically relevant regions of chemical space, for example natural product or drug space, to select scaffolds as starting points for the design and synthesis of small focused libraries with limited diversity. In this respect BIOS provides a conceptual alternative to other approaches... 

Yang SS, Cragg GM, Newman DJ, Bader JP (2001) Natural product-based anti-HIV drug discovery and development facilitated by the NCI development therapeutics program. J Nat Prod 64 265-277... 

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