Abstract

) The long term objective of this NCNPDDG is the identification of compounds suitable for development as antitumor agents. This is to be done by 1. utilizing existing, validated assay to guide the screening/isolation of novel DNA damaging agents, and inhibitors of DNA topoisomerase I, DNA topoisomerase II, DNA polymerase B and Myt1 kinase (Programs 1, 2 and 3) 2. developing new mechanism-based assays as high-throughput primary screens for natural products with potential activity in the treatment of cancer, including inhibitors of proliferation-linked signal transduction (Program 1) 3. fractionating lead extracts and characterizing isolated natural products derived from each of the assay systems as chemical entities and biological mediators (Programs 2 and 3) 4. developing and utilizing secondary discriminators to guide the focused identification of natural/products/structurally modified compounds predicted to have useful antitumor activity (Programs 1 and 3) 5. preparing in quantity and evaluating promising compounds in tumor cells (for mechanism, biochemical pharmacology, interaction with known antineoplastic agents) and in animal tumor models (Programs 1-3)

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program--Cooperative Agreements (U19)
Project #
5U19CA050771-12
Application #
6375851
Study Section
Special Emphasis Panel (ZCA1-SRRB-C (M2))
Program Officer
Lees, Robert G
Project Start
2000-09-30
Project End
2005-05-31
Budget Start
2001-09-26
Budget End
2002-05-31
Support Year
12
Fiscal Year
2001
Total Cost
$876,342
Indirect Cost

  Institution

Name
University of Virginia
Department
Chemistry
Type
Schools of Arts and Sciences
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