Biodiversity Conservation and Drug Discovery - Kingston Group

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Biodiversity Conservation and Drug Discovery

The tropical rain forests of the world represent one of the last preserves of biodiversity, and hold the potential for the discovery of new pharmaceuticals and other valuable products. Regrettably these forests are disappearing at a rapid rate as they are logged for timber or conversion to agricultural purposes. In an attempt to demonstrate the economic value of keeping these forests intact, we have joined with conservation, industrial, and botanical groups to develop a model program for drug discovery and biodiversity conservation in Madagascar. Plants are collected in the host country 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 the host country as an economic incentive to maintain their tropical forests. The new bioactive compounds below have all been isolated from plants collected in this program, and two of them are being investigated further as potential anticancer agents. We are partnered with Eisai Research Institute (ERI) in this work, and any compounds with significant anticancer activity will be offered to ERI for development.

Selected Publications

D. G. I. Kingston, M. Abdel-Kader, B.-N. Zhou, S.-W. Yang, J. M. Berger, H. van der Werff, J. S. Miller, R. Evans, R. Mittermeier, L. Famolare, M. Guerin-McManus, S. Malone, E. Moniz, J. H. Wisse, D. Vyas and J. J. K. Wright "The Suriname International Cooperative Group: Lessons From the First Five Years". Pharm. Biol. 1999, S37, 22-34.

M. S. Abdel-Kader, B. D. Bahler, S. Malone, M. C. M. Werkhoven, J. H. Wisse, K. Neddermann, I. Bursuker, and D. G. I. Kingston. "Bioactive Saponins from Swartzia schomburgkii from the Suriname Rain Forest." J. Nat. Prod. 2000, 63, 1461-1464.

A. A. L. Gunatilaka, J. M. Berger, R. Evans, J. S. Miller, J. H. Wisse, K. M. Neddermann, I. Bursuker, and D. G. I. Kingston "Isolation, Synthesis, and Structure-Activity Relationships of Bioactive Benzoquinones from Miconia lepidota from the Suriname Rain Forest." J. Nat. Prod. 2001, 64, 2-5.

M. Abdel-Kader, J. Hoch, J. Berger, R. Evans, J. S. Miller, J. H. Wisse, S. Mamber, J. M. Dalton, and D. G. I. Kingston "Two Bioactive Saponins from Albizia subdimidiata from the Suriname Rainforest." J. Nat. Prod. 2001, 64, 536-539.

D. G. I. Kingston "Biodiversity Conservation and Drug Discovery in Suriname: Explorations in Nature s Combinatorial Library." Pure Appl. Chem. 2001, 73, 595-599.

M. Abdel-Kader, J. M. Berger, C. Slebodnick, J. Hoch, S. Malone, J. H. Wisse, M. C. M. Werkhoven, S. Mamber, and D. G. I. Kingston, "Isolation and Absolute Configuration of ent-Halimane Diterpenoids from Hymenaea courbaril from the Suriname Rain Forest." J. Nat. Prod. 2002, 65, 11-15.

Y. Seo, J. M. Berger, J. Hoch, K. Neddermann, I. Bursuker, S. W. Mamber, and D. G. I. Kingston, "A New Triterpenoid Saponin from Pittosporum viridiflorum from the Madagascar Rainforest." J. Nat. Prod. 2002, 65, 65-68.

Y. Seo, J. Hoch, M. Abdel-Kader, S. Malone, I. Derveld, H. Adams, M. C. M. Werkhoven, J. H. Wisse, T. Glass, S. W. Mamber, J. M. Dalton, and D. G. I. Kingston, "Bioactive Saponins from Acacia tenuifolia from the Suriname Rainforest" J. Nat. Prod. 2002, 65, 170-174.

C. V. Sai Prakash, J. M. Hoch, C. R. Fairchild, K. A. Johnston, and D. G. I. Kingston, "Structure and Stereochemistry of New Cytotoxic Clerodane Diterpenoids from the Bark of Casearia lucida from the Madagascar Rainforest" J. Nat. Prod. 2002, 65, 100-107.

D. G. I. Kingston and D. J. Newman, "Mother Nature's Combinatorial Libraries: Their Influence on the Synthesis of Drugs" Current Opin. Drug Disc. Devel. 2002, 5, 304-316.

V. S. P. Chaturvedula, J. K. Schilling, and D. G. I. Kingston "New Cytotoxic Coumarins and Prenylated Benzophenone Derivatives from the bark of Ochrocarpus punctatus from the Madagascar Rainforest" J. Nat. Prod. 2002, 65, 965-972.

V. S. P. Chaturvedula, J. K. Schilling, J. Miller, R. Andriantsiferana, and D. G. I. Kingston "Two New Triterpene Esters from the Twigs of Brachylaena ramiflora from the Madagascar Rainforest" J. Nat. Prod. 2002, 65, 1222-1224.

V. S. P. Chaturvedula, J. K. Schilling, J. S. Miller, R. Andriantsiferana, and D. G. I. Kingston "New Cytotoxic Bis-5-Alkylresorcinol Derivatives from the Leaves of Oncostemon bojerianum from the Madagascar Rainforest" J. Nat. Prod. 2002, 65, 1627-1632.

V. S. P. Chaturvedula, J. K. Schilling, J. H. Wisse, J. S. Miller, R. Evans, and D. G. I. Kingston "A New Cytotoxic Limonoid from Odontadenia macrantha from the Suriname Rainforest" Mag. Reson. Chem. 2003, 41, 139-142.

V. S. P. Chaturvedula, J. K. Schilling, S. Malone, M. C. M. Werkhoven, J. H. Wisse, and D. G. I. Kingston "Two New Triterpene Acids from Manihot esculenta from the Suriname Rainforest" Planta Med. 2003, 69, 271-274.

V. S. P. Chaturvedula, J. K. Schilling, J. S. Miller, R. Andriantsiferana, V. E. Rasamison, and David G. I. Kingston, "New Cytotoxic Oleanane Saponins from the Infructescences of Polyscias amplifolia from the Madagascar Rainforest" Planta Med. 2003, 69, 440-444.

V. S. P. Chaturvedula, S. Sprague, J. K. Schilling, and D. G. I. Kingston, "New Cytotoxic Indole Alkaloids from Tabernaemontana calcarea from the Madagascar Rainforest" J. Nat. Prod. 2003, 66, 528-531.

V. S. P. Chaturvedula, J. K. Schilling, J. S. Miller, R. Andriantsiferana, V. E. Rasamison, and David G. I. Kingston "New Cytotoxic Alkaloids from the Wood of Vepris punctata from the Madagascar Rainforest" J. Nat. Prod. 2003, 66, 532-534.

R. B. Williams, J. Hoch, T. E. Glass, R. Evans, J. S. Miller, Jan H. Wisse, and D. G. I. Kingston, "A Novel Cytotoxic Guttiferone Analog from Garcinia macrophylla from the Suriname Rainforest." Planta Med. 2003, 69, 864-866.

V. S. P. Chaturvedula, Z. Gao, S. M. Hecht, S. H. Jones, and David G. I. Kingston, "A New Acylated Oleanane Triterpenoid from Couepia polyandra that Inhibits the Lyase Activity of DNA Polymerase-bð." J. Nat. Prod. 2003, 66, 1463-1465.

J. A. Clement, B. J. Yoder, and D. G. I. Kingston, "Natural Products as a Source of CNS Agents," Mini-Rev. Org. Chem. 2004, 1, 183-208.

S. Cao, S. J. K. Schilling, J. S. Miller, R. Andriantsiferana, V. E. Rasamison, D. G. I. Kingston, "Cytotoxic Compounds from Mundulea chapelieri from the Madagascar Rainforest" J. Nat. Prod. 2004, 67, 454-456.

V. S. P. Chaturvedula, J. K. Schilling, J. S. Miller, R. Andriantsiferana, V. E. Rasamison, and D. G. I. Kingston, "New Cytotoxic Terpenoids from the Wood of Vepris punctata from the Madagascar Rainforest" J. Nat. Prod. 2004, 67, 895-898.

S. Cao, R. C. Guza, J. S. Miller, R. Andriantsiferana, V. E. Rasamison, and D. G. I. Kingston, "Cytotoxic Triterpenoids from Acridocarpus vivy." J. Nat. Prod. 2004, 67, 986-989.

S. Cao, J. K. Schilling, J. S. Miller, A. Randrianasolo, R. Andriantsiferana, V. E. Rasamison, and D. G. I. Kingston. "New Cytotoxic Alkyl Phloroglucinols from Protorhus thouvenotii" Planta Med. 2004, 70, 683-684.

E. Adou, J. Hoch, S. Malone, M. C. M. Werkhoven, J. H. Wisse, and D. G. I. Kingston, "New Diterpenoids from a Dichapetalum sp. from the Suriname Rainforest." Manuscript in preparation for submission to J. Nat. Prod.