Department of Chemistry and Biochemistry, University of California, Santa Cruz, Santa Cruz, California 95064, United States.
J Nat Prod. 2011 Mar 25;74(3):341-51. doi: 10.1021/np100721g. Epub 2011 Jan 11.
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.
环二肽 Jasplakinolide（1）（又名 Jaspmamide），先前从海洋海绵 Jaspis splendens 中分离出来，是一种独特的细胞毒素和分子探针，通过稳定丝状肌动蛋白（F-actin）起作用。我们最近披露，1 的两种类似物， Jasplakinolides B（3）和 E，已提交给美国国立癌症研究所（NCI）的生物评估委员会，本研究的目的是重新研究来自斐济的 J. splendens 采集物，以寻找具有相似生物学特性的 Jasplakinolide 同系物。目前的努力已经提供了六个已知的 Jasplakinolide 类似物（4-7、9、10），两个需要修订的结构（8 和 14），以及四个新的 1 同系物（11-13、15），包括开链衍生物和具有修饰的β-酪氨酸残基的结构。化合物在 NCI 的 60 种细胞系筛选和 HCT-116 和 HeLa 细胞中的微丝破坏测定中进行了生物活性评估。这两个表型筛选提供了证据，表明每个细胞毒性类似物，包括 Jasplakinolide B（3），通过修饰微丝起作用。新结构 Jasplakinolide V（13）也已被 NCI 的生物评估委员会选中进行研究。此外，还介绍了 Jasplakinolide 集落形成剂量反应研究的结果。
