Abstract

) The long term objective of this Laboratory Program is the identification of compounds suitable for development as antitumor agents. During the project period, objectives include: (1) identifying mechanistically unique DNA damaging agents (2) obtaining more potent inhibitors of DNA polymerase beta so that it is possible to complete the testing of the hypothesis that these agents can potentiate the cytotoxic activity of antitumor agents that act by creating DNA lesions, and demonstrating the ability of such inhibitors to potentiate the antitumor activity of agents such as bleomycin, esperamicin and califcheamicin (3) fractionating prioritized extracts identified by Program 1 to isolate and structurally characterize the natural principle(s) (4) prioritizing the lead compounds identified by the studies outlined above and obtaining the most promising compounds in quantities sufficient for antitumor evaluation in experimental animal models/initial preclinical development.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA050771-13
Application #
6662766
Study Section
Project Start
2002-09-18
Project End
2003-05-31
Budget Start
Budget End
Support Year
13
Fiscal Year
2002
Total Cost
Indirect Cost

  Institution

Name
University of Virginia
Department
Type
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904

  Publications

Cao, Shugeng; Murphy, Brian T; Foster, Caleb et al. (2009) Bioactivities of simplified adociaquinone B and naphthoquinone derivatives against Cdc25B, MKP-1, and MKP-3 phosphatases. Bioorg Med Chem 17:2276-81
Clement, Jason A; Li, Mei; Hecht, Sidney M et al. (2006) Bioactive isomalabaricane triterpenoids from Rhabdastrella globostellata that stabilize the binding of DNA polymerase beta to DNA. J Nat Prod 69:373-6
Cao, Shugeng; Foster, Caleb; Brisson, Marni et al. (2005) Halenaquinone and xestoquinone derivatives, inhibitors of Cdc25B phosphatase from a Xestospongia sp. Bioorg Med Chem 13:999-1003
Cao, Shugeng; Foster, Caleb; Lazo, John S et al. (2005) Four diterpenoid inhibitors of Cdc25B phosphatase from a marine anemone. Bioorg Med Chem 13:5830-4
Chaturvedula, V S Prakash; Gao, Zhijie; Jones, Shannon H et al. (2004) A new ursane triterpene from Monochaetum vulcanicum that inhibits DNA polymerase beta lyase. J Nat Prod 67:899-901
Chaturvedula, V S Prakash; Zhou, Bing-Nan; Gao, Zhijie et al. (2004) New lupane triterpenoids from Solidago canadensis that inhibit the lyase activity of DNA polymerase beta. Bioorg Med Chem 12:6271-5
Prakash Chaturvedula, V S; Hecht, Sidney M; Gao, Zhijie et al. (2004) New neolignans that inhibit DNA polymerase beta lyase. J Nat Prod 67:964-7
Prakash Chaturvedula, V S; Schilling, Jennifer K; Johnson, Randall K et al. (2003) New cytotoxic lupane triterpenoids from the twigs of Coussarea paniculata. J Nat Prod 66:419-22
Prakash Chaturvedula, V S; Gao, Zhijie; Hecht, Sidney M et al. (2003) A new acylated oleanane triterpenoid from Couepia polyandra that inhibits the lyase activity of DNA polymerase beta. J Nat Prod 66:1463-5
Zhou, B N; Johnson, R K; Mattern, M R et al. (2001) The first naturally occurring Tie2 kinase inhibitor. Org Lett 3:4047-9

Showing the most recent 10 out of 14 publications