Biostructural features of additional jasplakinolide (jaspamide) analogues

J Nat Prod. 2011 Mar 25;74(3):341-51. doi: 10.1021/np100721g. Epub 2011 Jan 11.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Actins / metabolism
  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification
  • Antineoplastic Agents / pharmacology*
  • Cytotoxins / chemistry
  • Cytotoxins / isolation & purification
  • Cytotoxins / pharmacology*
  • Depsipeptides / chemistry
  • Depsipeptides / isolation & purification
  • Depsipeptides / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Fiji
  • HCT116 Cells
  • HeLa Cells
  • Humans
  • Marine Biology
  • Molecular Structure
  • National Cancer Institute (U.S.)
  • Peptides, Cyclic
  • Stereoisomerism
  • United States

Substances

  • Actins
  • Antineoplastic Agents
  • Cytotoxins
  • Depsipeptides
  • Peptides, Cyclic
  • jaspamide B
  • jasplakinolide E
  • jasplakinolide V
  • jasplakinolide