Anticancer Natural Products Drug Discovery

//Anticancer Natural Products Drug Discovery
Anticancer Natural Products Drug Discovery2019-01-30T21:45:27+00:00

Using a novel bioassay to discover inhibitors of the proteasome

Natural products have a proven track record as sources of new anticancer agents.  Thus Newman and Cragg (2012) showed that 47% of anticancer agents developed from the 1940s to 2006 are natural products or derived directly from natural products.  Natural products, with their structural and stereochemical complexity, provide an alternate source of potential drugs and also can serve as a starting point for synthetic chemistry efforts.  As one example, statistical comparisons between the properties of drugs, natural products, and compounds from combinatiorial libraries show that there is a much higher correlation between the properties of drugs and those of natural products than between those of drugs and compounds from combinatorail libraries (Feher and Schmidt, 2003).  The study of natural products as lead compounds for drug development is thus likely to continue to prove richly rewarding.

Our group has searched for novel natural anticancer agents from the plants, marine, and microbial species of Madagascar, as well as from the Merck collection of natural product extracts.  The primary tool was a bioassay against the A2780 ovarian cancer cell line.  Examples of compounds isolated are shown below.  Both the ipomoeassins and the schweinfurthins are promising lead compounds.

iposoeassins and schweinfurthins

Selected references

Newman, D. J.; Cragg, G. M. Natural products as sources of new drugs over the 30 years from 1981 to 2010. J. Nat. Prod. 2012, 75, 311-355.

Feher, M.; Schmidt, J. M. Property distributions: Differences between drugs, natural products, and molecules from combinatorial chemistry. J. Chem. Inf. Comput. Sci. 2003, 43, 218-227.

Cao, S.; Guza, R. C.; Wisse, J. H.; Evans, R.; van der Werff, H.; Miller, J. S.; Kingston, D. G. I. Ipomoeassins A-E, five new cytotoxic macrocyclic glycoresins, from the leaves of Ipomoea squamosa from the Suriname rainforest. J. Nat. Prod. 2005, 68, 487-492.

Yoder, B. J.; Cao, S.; Norris, A.; Miller, J. S.; Ratovoson, F.; Razafitsalama, J.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. Antiproliferative prenylated stilbenes and flavonoids from Macaranga alnifolia from the Madagascar rainforest. J. Nat. Prod. 2007, 70, 342-346.