Discovery of structurally novel and potentially very important anticancer drugs from animal, plant and microorganism sources followed by their synthesis and/or structural modification will form the sharply focused objective of this research for the U.S. National Cancer Institute (NCI) . Special emphasis will be placed on new antineoplastic substances either isolated based on molecular target bioassays or subsequently displaying such potent antiangiogenesis, tubulin and/or various cancer-implicated kinase (cyclin-dependent, protein kinase C, tyrosine kinase and telomerase) properties as well as exceptionally strong antineoplastic activity. Additional emphasis will be placed on further research necessary to advancing the expanding clinical trials of bryostatin 1, the dolastatins, and others we discovered such as the powerful cancer antiangiogenesis drug combretastatin A-4 phosphate. vigorous parallel research will be strongly focused on the isolation, characterization, and structural determination of new and potentially useful anticancer drugs from confirmed active extracts of marine invertebrates (and vertebrates) , marine and terrestrial plants, and marine as well as terrestrial microorganisms. Only those species that give maximum promise of yielding new drugs with potential clinical activity will be pursued. The proposed research will provide great assistance to the DCTD/NCI in selecting new anticancer drug candidates and speeding their development toward clinical trial. In summary, the proposed research will be sharply aimed at the discovery and very rapid development of new anticancer drugs for the NCI programs directed at improving human cancer treatments.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA090441-05
Application #
6858674
Study Section
Experimental Therapeutics Subcommittee 1 (ET)
Program Officer
Fu, Yali
Project Start
2001-04-01
Project End
2006-03-31
Budget Start
2005-04-01
Budget End
2006-03-31
Support Year
5
Fiscal Year
2005
Total Cost
$780,071
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Other Health Professions
Type
Schools of Arts and Sciences
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Pettit, George R; Searcy, Justin D; Tan, Rui et al. (2016) Antineoplastic Agents. 585. Isolation of Bridelia ferruginea Anticancer Podophyllotoxins and Synthesis of 4-Aza-podophyllotoxin Structural Modifications. J Nat Prod 79:507-18
Pettit, George R; Smith, Thomas H; Arce, Pablo M et al. (2015) Antineoplastic agents. 599. Total synthesis of dolastatin 16. J Nat Prod 78:476-85
Pettit, George R; Xu, Jun-Ping; Chapuis, Jean-Charles et al. (2015) The Cephalostatins. 24. Isolation, Structure, and Cancer Cell Growth Inhibition of Cephalostatin 20. J Nat Prod 78:1446-50
Pettit, George R; Moser, Bryan R; Herald, Delbert L et al. (2015) The Cephalostatins. 23. Conversion of Hecogenin to a Steroidal 1,6-Dioxaspiro[5.5]nonane Analogue for Cephalostatin 11. J Nat Prod 78:1067-72
Pettit, George R; Arce, Pablo M; Chapuis, Jean-Charles et al. (2015) Antineoplastic agents. 600. From the South Pacific Ocean to the silstatins. J Nat Prod 78:510-23
Pettit, George R; Melody, Noeleen; Hempenstall, Frank et al. (2014) Antineoplastic agents. 595. Structural modifications of betulin and the X-ray crystal structure of an unusual betulin amine dimer. J Nat Prod 77:863-72
Pettit, George R; Tang, Yuping; Zhang, Qingwen et al. (2013) Isolation and structures of axistatins 1-3 from the Republic of Palau marine sponge Agelas axifera Hentschel . J Nat Prod 76:420-4
Lubahn, Cheri; Schaller, Jill A; Shewmacker, Eric et al. (2012) Preclinical efficacy of sodium narcistatin to reduce inflammation and joint destruction in rats with adjuvant-induced arthritis. Rheumatol Int 32:3751-60
Pettit, George R; Moser, Bryan R; Mendonça, Ricardo F et al. (2012) The cephalostatins. 22. synthesis of bis-steroidal pyrazine pyrones (1). J Nat Prod 75:1063-9
Pettit, George R; Tan, Rui; Bao, Guan-Hu et al. (2012) Antineoplastic agents. 587. Isolation and structure of 3-epipancratistatin from Narcissus cv. Ice Follies. J Nat Prod 75:771-3

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