University Distinguished Professor,
Bioorganic and Natural Products Chemistry
E-mail: dkingston@vt.edu
Office: 3111 Hahn Hall
Phone: 540-231-6570
Fax: 540-231-3255
Group Web Pages: http://www.kingston.chem.vt.edu
Research Video Clip http://www.chem.vt.edu/faculty/videos/Kingston.wmv
Education, Honors and Awards
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
Research Interests
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).
Selected Publications
- 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.
- 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.
- 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.
- 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.
- 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.
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