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, 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 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 Inc. in this work, and any compounds with significant anticancer activity will be offered to Eisai for development.

Selected Publications

Harinantenaina, L.; Brodie, P. J.; Slebodnick, C.; Callmander, M. W.; Rakotobe, E.; Randrianasolo, S.; Randrianaivo, R.; Rasamison, V. E.; TenDyke, K.; Shen, Y.; Suh, E. M.; Kingston, D. G. I. Antiproliferative Compounds from Pongamiopsis pervilleana from the Madagascar Dry Forest. J. Nat. Prod. 2010, 73, 1559-1562.

Murphy, B. T.; Cao, S.; Brodie, P.; Maharavo, J.; Andriamanantoanina, H.; Ravelonandro, P.; Kingston, D. G. I. Antiproliferative Bistramides from Trididemnum cyclops from Madagascar. J. Nat. Prod. 2009, 72, 1338-1340.

Cao, S.; Murphy, B. T.; Foster, C.; Lazo, J. S.; Kingston, D. G. I. Bioactivities of Simplified Adociaquinone B and Naphthoquinone Derivatives against Cdc25B, MKP-1, and MKP-3 Phosphatases. Bioorg. Med. Chem. 2009, 17, 2276-2281.

Cao, S.; Brodie, P.; Callmander, M.; Randrianaivo, R.; Razafitsalama, J.; Rakotobe, E.; Rasamison, V. E.; TenDyke, K.; Shen, Y.; Suh, E. M.; Kingston, D. G. I. Antiproliferative Triterpenoid Saponins of Dodonaea viscosa from the Madagascar Dry Forest. J. Nat. Prod. 2009, 72, 1705-1707.

Murphy, B. T.; Brodie, P. J.; Slebodnick, C.; Miller, J. S.; Birkinshaw, C.; Randrianjanaka, L. M.; Andriantsiferana, R.; Rasamison, V. E.; TenDyke, K.; Suh, E. M.; Kingston, D. G. I. Antiproliferative Limonoids of a Malleastrum sp. from the Madagascar Rainforest. J. Nat. Prod. 2008, 71, 325-329.

Kingston, D. G. I. A natural love of natural products. J. Org. Chem. 2008, 73, 3975-3984.

Yoder, B. J.; Cao, S.; Norris, A.; Miller, J. S.; Ratovoson, F.; Razafitsalama, J.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. Antiproliferative Prenylated Stilbenes and Flavonoids from Macaranga alnifolia from the Madagascar Rainforest. J. Nat. Prod. 2007, 70, 342-346.

Williams, R. B.; Norris, A.; Miller, J. S.; Birkinshaw, C.; Ratovoson, F.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. Cytotoxic Clerodane Diterpenoids and Their Hydrolysis Products from Casearia nigrescens from the Rainforest of Madagascar. J. Nat. Prod. 2007, 70, 206-209.

Karkare, S.; Adou, E.; Cao, S.; Brodie, P. J.; Miller, J. S.; Andrianjafy, N. M.; Razafitsamala, J.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. Cytotoxic Cardenolide glycosides of Roupellina (Strophanthus) boivinii from the Madagascar Rainforest. J. Nat. Prod. 2007, 70.

Cao, S.; Norris, A.; Wisse, J. H.; Miller, J. S.; Evans, R.; Kingston, D. G. I. Ipomoeassin F, a New Cytotoxic Macrocyclic Glycoresin from the Leaves of Ipomoea squamosa from the Suriname Rain Forest. Nat. Prod. Res. 2007, 21, 872-876.

Cao, S.; Norris, A.; Miller, J. S.; Ratovoson, F.; Razafitsalama, J.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. Cytotoxic Triterpenoid Saponins of Albizia gummifera from the Madagascar Rain Forest. J. Nat. Prod. 2007, 70, 361-366.

Cao, S.; Brodie, P. J.; Miller, J. S.; Ratovoson, F.; Callmander, M.; Randrianasolo, S.; Rakotobe, E.; Rasamison, V. E.; Kingston, D. G. I. Antiproliferative Cardenolides of Elaeodendron cf. orientale Jacq. from the Madagascar Rain Forest. J. Nat. Prod. 2007, 70, 1064-1066.

Cao, S.; Brodie, P. J.; Miller, J. S.; Randrianaivo, R.; Ratovoson, F.; Birkinshaw, C.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. Antiproliferative Xanthones of Terminalia calcicola from the Madagascar Rain Forest. J. Nat. Prod. 2007, 70, 679-681.

Williams, R.; Norris, A.; Miller, J. S.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. Two New Cytotoxic Naphthaquinones from Mendoncia cowanii from the Rainforest of Madagascar. Planta Med. 2006, 72, 564-566.

Clement, J. A.; Li, M.; Hecht, S. M.; Kingston, D. G. I. Bioactive Isomalabaricane Triterpenoids from Rhabdastrella globostellata that Stabilize the Binding of DNA Polymerase beta to DNA. J. Nat. Prod. 2006, 69, 373-376.

Cao, S.; Radwan, M. M.; Norris, A.; Miller, J. S.; Ratovoson, F.; Andrianjafy, M.; Andriantsiferana, R.; Rasamison, V. E.; Rakotonandrasana, S.; Kingston, D. G. I. Cytotoxic Compounds from Didymochlaena sp. (Dryopteridaceae) from the Madagascar Rain Forest. J. Nat. Prod. 2006, 69, 284-286.

Zhou, B.-N.; Tang, S.; Johnson, R. K.; Mattern, M. R.; Lazo, J. S.; Sharlow, E. R.; Harich, K.; Kingston, D. G. I. New Glycolipid Inhibitors of Myt1 Kinase. Tetrahedron 2005, 61, 883-887.

Williams, R. B.; Norris, A.; Slebodnick, C.; Merola, J. S.; Miller, J. S.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. Cytotoxic Sesquiterpene Lactones from Vernonia pachyclada from the Madagascar Rainforest. J. Nat. Prod. 2005, 68, 1371-1374.

Murphy, B. T.; Cao, S.; Norris, A.; Miller, J. S.; Ratovoson, F.; Andriantsiferana, R.; Rasamison, V. E.; Kingston, D. G. I. Cytotoxic Flavanones of Schizolaena hystrix from the Madagascar Rainforest. J. Nat. Prod. 2005, 68, 417-419.

Kingston, D. G. I.; Newman, D. J. Natural Products as Drug Leads; An Old Process or the New Hope for Drug Discovery? iDrugs 2005, 8, 990-992.

Kingston, D. G. I.; Newman, D. J. The Search for Novel Drug Leads for Predominately Antitumor Therapies by Utilizing Mother Nature's Pharmacophoric Libraries. Drug Disc. Develop. 2005, 8, 207-227.

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.

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.

Adou, E.; Williams, R.; Schilling, J. K.; Malone, S.; Meyer, J.; Wisse, J. H.; Frederik, D.; Koese, D.; Werkhoven, M. C. M.; Snipes, C. E.; Werk, T. L.; Kingston, D. G. I. Cytotoxic Diterpenoids from Two Lianas from the Suriname Rainforest. Bioorg. Med. Chem. 2005, 13, 6009-6014.

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

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

Chaturvedula, V. S. P.; Farooq, A.; Schilling, J. K.; Malone, S.; Derveld, I.; Werkhoven, M. C. M.; Wisse, J. H.; Ratsimbason, M.; Kingston, D. G. I. New Eudesmane Derivatives from Melampodium camphoratum from the Suriname Rainforest. J. Nat. Prod. 2004, 67, 2053-2057.

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