The objectives of this research are to identify, isolate and determine the structure of cytotoxic and in vivo tumor inhibitory compounds from a variety of marine organisms. The primary sources for new compounds will be sponges, ascidians, and coelenterates. In addition, marine bacteria isolated from sponges and some other marine sources will be cultured and extracted to search for potential antitumor compounds. Isolation will be guided by activity testing provided by the National Cancer Institute using in vivo (PS) and/or in vitro (KB, P388, L1210) test systems. To the extent possible compounds will be isolated in sufficient quantities to conduct in vivo activity testing. Antitumor activity enhancement will be sought through structural modification of some of the active compounds isolated. A variety of established, modern separation techniques will be used to isolate compounds, and structures will be determined by single cystal x-ray analysis and/or conventional spectroscopic methods. The structures of chemically novel compounds obtained incidental to the primary objective will be investigated to the extent possible. The long term goal of this project is to discover clinically useful anticancer agents.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Project (R01)
Project #
5R01CA017256-11
Application #
3164625
Study Section
Bio-Organic and Natural Products Chemistry Study Section (BNP)
Project Start
1978-08-01
Project End
1989-03-31
Budget Start
1987-04-01
Budget End
1988-03-31
Support Year
11
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Oklahoma Norman
Department
Type
Schools of Arts and Sciences
DUNS #
848348348
City
Norman
State
OK
Country
United States
Zip Code
73019
Yatsunami, J; Fujiki, H; Suganuma, M et al. (1991) Binding competition of okadaic acid derivatives to anti-okadaic acid antibody. Toxicon 29:1409-12
Santavy, D L; Willenz, P; Colwell, R R (1990) Phenotypic study of bacteria associated with the caribbean sclerosponge, Ceratoporella nicholsoni. Appl Environ Microbiol 56:1750-62
Fujiki, H; Suganuma, M; Nishiwaki, S et al. (1990) A new pathway of tumor promotion by the okadaic acid class compounds. Adv Second Messenger Phosphoprotein Res 24:340-4
Nishiwaki, S; Fujiki, H; Suganuma, M et al. (1990) Structure-activity relationship within a series of okadaic acid derivatives. Carcinogenesis 11:1837-41
Ksebati, M B; Schmitz, F J (1988) Sesquiterpene furans and thiosesquiterpenes from the nudibranch Ceratosoma brevicaudatum. J Nat Prod 51:857-61
Schmitz, F J; Chang, J C (1988) Sesterterpenes from a Pacific sponge, Carteriospongia flabellifera. J Nat Prod 51:745-8
Schmitz, F J; Gunasekera, S P; Lakshmi, V et al. (1985) Marine natural products: pyrrololactams from several sponges. J Nat Prod 48:47-53