期刊
JOURNAL OF NATURAL PRODUCTS
卷 74, 期 3, 页码 341-351出版社
AMER CHEMICAL SOC
DOI: 10.1021/np100721g
关键词
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资金
- NIH [RO1 CA 047135, U19 CA52955, S10 RR19918]
- NSF [CHE 0342912]
- U.S. Civilian Research and Development Foundation [GTR-G7-044]
- California Institute for Quantitative Biomedical Research
The cydodepsipepdde jasplakinolide (1) (aka jaspamide), isolated previously from the marine sponge Jaspis splendens, is a unique cytotoxin and molecular probe that operates through stabilization of filamentous actin (F-actin). We have recently disclosed that two analogues of 1, jasplakinolides B (3) and E, were referred to the National Cancer Institute's (NCI) Biological Evaluation Committee, and the objective of this study was to reinvestigate a Fijian collection of J. splendens in an effort to find jasplakinolide congeners with similar biological properties. The current efforts have afforded six known jasplakinolide analogues (4-7, 9, 10), two structures requiring revision (8 and 14), and four new congeners of 1 (11-13, 15) including open-chain derivatives and structures with modified beta-tyrosine residues. Compounds were evaluated for biological activity in the NCI's 60 cell line screen and in a microfilament disruption assay in both HCT-116 and HeLa cells. These two phenotypic screens provide evidence that each cytotoxic analogue, including jasplakinolide B (3), operates by modification of microfilaments. The new structure jasplakinolide V (13) has also been selected for study by the NCI's Biological Evaluation Committee. In addition, the results of a clonogenic dose-response study on jasplakinolide are
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