Biostructural features of additional jasplakinolide (jaspamide) analogues.
J Nat Prod
; 74(3): 341-51, 2011 Mar 25.
Article
em En
| MEDLINE
| ID: mdl-21241058
ABSTRACT
The cyclodepsipeptide 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 ß-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 presented.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Citotoxinas
/
Depsipeptídeos
/
Antineoplásicos
Limite:
Animals
/
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
J Nat Prod
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos