Affordable Access

deepdyve-link
Publisher Website

Biostructural features of additional jasplakinolide (jaspamide) analogues.

Authors
  • Kr, Watts
  • Bi, Morinaka
  • T, Amagata
  • Sj, Robinson
  • K, Tenney
  • Wm, Bray
  • Nc, Gassner
  • Rs, Lokey
  • J, Media
  • Fa, Valeriote
  • P, Crews
Type
Published Article
Journal
Journal of Natural Products
Publisher
American Chemical Society
Volume
74
Issue
3
Pages
341–351
Identifiers
DOI: 10.1021/np100721g
Source
UCSC Cancer biomedical-ucsc
License
Unknown

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 β-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.

Report this publication

Statistics

Seen <100 times