B.A., Cambridge University, 1960
Ph.D., Cambridge University, 1963
Research Fellow, Queens' College, Cambridge, 1962-66
Research Associate and Fulbright Grantee, Massachusetts Institute of Technology, 1963-64
NATO Fellow, Cambridge University, 1964-66

Natural products have made a major contribution to drug discovery and especially to cancer chemotherapy, with Taxol (1) being the best-selling anticancer drug in history. Research in our group is centered around the chemistry of biologically active natural products related to cancer, with major areas being the chemistry and mechanism of action of the anti-cancer agent Taxol, the discovery of new anticancer agents from plants, and biodiversity conservation and drug discovery in tropical rain forests. In the Taxol area we are studying the nature of its binding to microtubules in collaboration with Dr. Susan Bane, and we are also looking at structure-activity relationships with the aim of designing potent and readily accessible Taxol analogs. In the natural products area we are involved in a search for novel anti-cancer agents from Nature in two major collaborative projects with investigators from the University of Virginia, Glaxo SmithKline Pharmaceuticals, and Bristol-Myers Squibb Pharmaceuticals. Plant and marine extracts are fractionated using selective bioassays to guide the fractionation, and structure elucidation is carried out primarily by spectroscopic methods. These projects emphasize isolation and structure elucidation, but synthetic approaches to the isolated compounds are also employed where feasible, to obtain adequate material for biological testing. Compounds isolated range from simple quinones to diterpenoids (2), saponins (3), alkaloids (4), and complex lipids (5).

   

1. Ganesh, T.; Guza, R. C.; Bane, S.; Ravindra, R.; Shanker, N.; Lakdawala, A. S.; Snyder, J. P.; Kingston, D. G. I. The Bioactive Taxol Conformation on ß-tubulin: Experimental Evidence from Highly Active Constrained Analogs. Proc. Natl. Acad. Sci USA, 2004, 101, 10006-10011.
2. Cao, S.; Foster, C.; Brisson, M.; Lazo, J. S.; Kingston, D. G. I. Halenaquinone and Xestoquinone Derivatives, Inhibitors of Cdc25B Phosphatase from a Xestospongia sp. Bioorg. Med. Chem. 2005, 13, 999-1003.
3. 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.
4. Paik, Y.; Yang, C.; Metaferia, B.; Tang, S.; Bane, S.; Ravindra, R.; Shanker, N.; Alcarez, A. A.; Johnson, S. A.; Schaefer, J J.; O'Connor, R. D.; Cegelski, L.; Snyder, J. P.; Kingston, D. G. I. REDOR NMR Studies of the Tubulin-Bound Paclitaxel Conformation. J. Am. Chem. Soc. 2007, 129, 361-370.
5. Ganesh, T.; Yang, C.; Norris, A.; Glass, T.; Bane, S.; Ravindra, R.; Banerjee, A.; Metaferia, B.; Thomas, S. L.; Giannakakou, P.; Alcaraz, A. A.; Lakdawala, A. S.; Snyder, J. P.; Kingston, D. G. I. Evaluation of the Tubulin-Bound Paclitaxel Conformation: Synthesis, Biology and SAR Studies of C-4 to C-3' Bridged Paclitaxel Analogs. J. Med. Chem., 2007, 50, 713-725.