Natural Product Oncology

Importance of natural products in oncology

More than 60% of anticancer drugs are of natural origin, or resulting from modifications of natural products (NP). Since a few years there is a regain of interests in natural products: since 2007, a new NP derivative has been approved every year for the treatment of cancers. The features and advantages of NP vs. fully synthetic small molecules (SMM) are the following:

- NP were selected by evolution to reach their molecular target within cells,

-NP target more often than SMM proteins with a high number of protein-protein functional interactions, which interrupts critical signaling pathways,

- NP usually incorporate more oxygen atoms, more stereogenic centers, more fused rings than SMM,

- on the opposite NP in general include fewer nitrogen atoms, rotatable bonds and aromatic rings than SMM,

- deep analyses of the structural and physical features of NP show that they occupy unusual part of the chemical space, indicating a much larger diversity in their structure and properties compared to those of « classical » synthetic medicines. The complexity of these structures explain also why NP are usually very selective toward a very small number of pharmacological targets.

 

Review from our lab on anticancer natural products

Cancer wars: Natural products strike back. Basmadjian, C.; Zhao, Q.; Djehal, A.; Bentouhami, E.; Nebigil, CG.; Johnson, RA., Serova, M.; de Gramont, A.; Faivre, S.; Raymond, E.; Désaubry, L. Frontiers Chem. 2, article 20 (2014).

 

Selected books, reviews and blogs on anticancer natural products

     Anticancer Agents from Natural Products. Edited by David G.I. Kingston, Gordon M. Cragg, and David J. Newman; CRC Press 2005.

     Drug discovery and natural products: End of an era or an endless frontier? Li JW-H, Vederas. JC. Science 325: 161-165 (2009).

     Modern natural products drug discovery and its relevance to biodiversity conservation. Kingston DG. J Nat Prod. 74: 496-511 (2011).

     Distinct biological network properties between the targets of natural products and disease genes. Dancík V, Seiler KP, Young DW, Schreiber SL, Clemons PA. J Am Chem Soc. 2010; 132: 9259-61.

     Activity-based protein profiling for natural product target discovery. Krysiak J, Breinbauer R. Top Curr Chem. 2012; 324:43-84.

      Charting, navigating, and populating natural product chemical space for drug discovery. Lachance H, Wetzel S, Kumar K, Waldmann H. J Med Chem. 55: 5989-6001 (2012).

     Recasting natural product research. Sheridan C. Nat Biotechnol. 30: 385-7 (2012).

     Discovery and development of natural product-derived chemotherapeutic agents based on a medicinal chemistry approach. Lee K-H. Journal of Natural Products 73: 500-516 (2010).

     The art and science of total synthesis at the dawn of the twenty-first century. Nicolaou KC, Vourloumis D, Winssinger N, Baran PS. Angew. Chem. Int. Ed. Engl. 39: 44-122 (2000).

     Naturalproductman’s blog. A great blog about the chemistry of natural products.