University Distinguished Professor of Chemistry
Research Focus
Drug Discovery and Biodiversity Conservation in Madagascar
Natural products have provided over a third of currently used pharmaceuticals, and the tropical rain forests of the world represent a great and largely untapped source of new natural products; examples of some of the compounds isolated in the Kingston group are shown below. Regrettably these forests are disappearing at a rapid rate as they are logged for timber or conversion to agricultural purposes. We have joined with conservation, industrial, and botanical groups to develop a model program for drug discovery and biodiversity conservation in Madagascar. Plants, marine organisms, and microbial species are collected in Madagascar and screened for bioactivity at Virginia Tech, and those with anticancer activity or CNS activity are studied in our laboratories. We have also helped to set up a malaria screening facility in Madagascar, and we are working to isolate antimalarial compounds in collaboration with our Malagasy colleagues. Any royalties from the resulting drugs will be shared with Madagascar as an economic incentive to maintain their tropical forests. The new bioactive compounds below have all been isolated from plants collected in this program. We are partnered with Eisai Inc. in this work, and any compounds with significant anticancer activity will be offered to Eisai for development.
Chemistry and Drug Delivery of Paclitaxel
The complex diterpenoid natural product taxol is an exciting anti-cancer drug that is currently in clinical use against ovarian and breast cancer. It does have some significant side-effects, and we are working with CytImmune Sciences Inc. to develop a gold nanoparticle approach to drug delivery. Preliminary results are encouraging, and one of the agents we have helped develop is approximately twentyfold more potent than paclitaxel itself. This project blends synthesis and biological studies to improve on one of the most important new anti-cancer natural products of the past 30 years.
Selected Publications
Kingston, D. G. I.; Snyder, J. P. The Quest for a Simple Bioactive Analog of Paclitaxel as a Potential Anticancer Agent. Acc. Chem. Res. 2014, 47, 2682–2691. DOI: 10.1021/ar500203h. PMCID: PMC4139185.
Dai, Yumin; Harinantenaina, Liva; Bowman, Jessica D.; Da Fonseca, Isabel Osorio; Brodie, Peggy J.; Goetz, Michael; Cassera, Maria B.; Kingston, David G. I. Isolation of Antiplasmodial Anthraquinones from Kniphofia ensifolia, and Synthesis and Structure-activity Relationships of Related Compounds. Bioorg. Med. Chem. 2014, 22, 269-276. PMCID: PMC3919637
Liva Harinantenaina, Jessica D. Bowman, Peggy J. Brodie, Carla Slebodnick, Martin W. Callmander, Etienne Rakotobe, Richard Randrianaivo, Vincent E. Rasamison, Alexander Gorka, Paul D. Roepe, Maria B. Cassera, and David G. I. Kingston, Antiproliferative and antiplasmodial dimeric phloroglucinols from Mallotus oppositifolius from the Madagascar Dry Forest. J. Nat. Prod., 2013, 76, 388-393. PMCID:PMC3606680.
David G. I. Kingston “Modern Natural Products Drug Discovery and its Relevance to Biodiversity Conservation” J. Nat. Prod. 2011, 74, 496-511. PMCID: PMC3061248
Y. Paik, C. Yang, B. Metaferia, S. Tang, S. Bane, R. Ravindra, N. Shanker, A. A. Alcarez, S. A. Johnson, J. Schaefer, R. D. O’Connor, L. Cegelski, J. P. Snyder, and D. G. I. Kingston. “Rotational-Echo Double-Resonance NMR Distance Measurements for the Tubulin-Bound Paclitaxel Conformation.” J. Am. Chem. Soc. 2007, 129, 361-370. PMCID: PMC2432525