Continued discovery of novel and potentially important cancer chemotherapeutic drugs from animal and plant sources will form the sharply focused objective of the overall Outstanding Investigator Grant (OIG) program with the National Cancer Institute (NCI). In order to provide the best choices for eventual clinical trial among the very important bryostatins, dolastatins, pancratistatin and the phyllanthostatins (phyllanthoside) recently discovered in our institute's collaborative research programs with the NCI, increased efforts will be devoted to uncovering additional members of each series and subjecting them to structural elucidation. While this important research is in progress a long-term study directed at the isolation, characterization and structural elucidation of new and potentially useful anticancer drugs from marine animals and plants will be continued. Financial support provided by the OIG program would be used to isolate and characterize such new cancer chemotherapeutic drugs from confirmed active extracts of marine invertebrates and vertebrates as well as marine terrestrial plants. The principal focus would be upon marine animal and plant species yielding extracts with an outstanding level of confirmed activity (T/C >150) in the NCI's murine P-388 lymphocytic leukemia, the NCI human caner cell systems, and later using, in part, new micro-organism and biochemical type preselection methods now under evaluation. Only those species that give maximum promise of yielding new drugs at a potential clinical level of interest will be pursued as part of the OIG research. Other such leads of a lesser priority will be pursued with any other financial support that might be available at that time. Because of 30 years spent building the foundation for this anticancer drug discovery research, a good number of exceedingly promising animal and plant species have already been uncovered and will be used along with newly developed leads to maintain a very productive output of potentially useful antineoplastic substances of unique structure. The OIOG program proposed will be of great assistance to the NCI in selecting new anticancer drug candidates and speeding their development toward clinical trial. In summary, the overall OIG program will be sharply focused on the discovery and very rapid development of new anticancer and HIV drugs for the national Cancer Institute's programs directed at improving human cancer and AIDS treatment.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Unknown (R35)
Project #
1R35CA044344-01A1
Application #
3479516
Study Section
(SRC)
Project Start
1989-06-01
Project End
1996-05-31
Budget Start
1989-06-01
Budget End
1990-05-31
Support Year
1
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Type
Schools of Arts and Sciences
DUNS #
188435911
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Kedei, Noemi; Kraft, Matthew B; Keck, Gary E et al. (2015) Neristatin 1 provides critical insight into bryostatin 1 structure-function relationships. J Nat Prod 78:896-900
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; Minardi, Mathew D; Hogan, Fiona et al. (2010) An efficient synthetic strategy for obtaining 4-methoxy carbon isotope labeled combretastatin A-4 phosphate and other Z-combretastatins. J Nat Prod 73:399-403
Pettit, George R; Knight, John C; Herald, Delbert L et al. (2009) Antineoplastic agents. 570. Isolation and structure elucidation of bacillistatins 1 and 2 from a marine Bacillus silvestris. J Nat Prod 72:366-71
Pettit, Robin K; Pettit, George R; Hamel, Ernest et al. (2009) E-Combretastatin and E-resveratrol structural modifications: antimicrobial and cancer cell growth inhibitory beta-E-nitrostyrenes. Bioorg Med Chem 17:6606-12
Pettit, George R; Ducki, Sylvie; Eastham, Stephen A et al. (2009) Antineoplastic agents. 454. Synthesis of the strong cancer cell growth inhibitors trans-dihydronarciclasine and 7-deoxy-trans-dihydronarciclasine (1a). J Nat Prod 72:1279-82
Pettit, George R; Hu, Shougang; Knight, John C et al. (2009) Antineoplastic agents. 571. Total synthesis of bacillistatin 2. J Nat Prod 72:372-9
Brennan, Mary R; Costello, Catherine E; Maleknia, Simin D et al. (2008) Stylopeptide 2, a proline-rich cyclodecapeptide from the sponge Stylotella sp. J Nat Prod 71:453-6
Pettit, George R; Hogan, Fiona; Xu, Jun-Ping et al. (2008) Antineoplastic agents. 536. New sources of naturally occurring cancer cell growth inhibitors from marine organisms, terrestrial plants, and microorganisms(1a,). J Nat Prod 71:438-44
Pettit, George R; Smith, Thomas H; Feng, Song et al. (2007) Antineoplastic agents. 561. Total synthesis of respirantin. J Nat Prod 70:1073-83

Showing the most recent 10 out of 154 publications