Sponge-derived fijianolide polyketide class: further evaluation of their structural and cytotoxicity properties

J Med Chem. 2007 Aug 9;50(16):3795-803. doi: 10.1021/jm070410z. Epub 2007 Jul 10.

Abstract

The sponge-derived polyketide macrolides fijianolides A (1) and B (2), isolaulimalide and laulimalide, have taxol-like microtubule-stabilizing activity, and the latter exhibits potent cytotoxicity. Insight on the biogeographical and phenotypic variations of Cacospongia mycofijiensis is presented that will enable a future study of the biosynthetic pathway that produces the fijianolides. In addition to fijianolides A and B, six new fijianolides, D-I (7-12), were isolated, each with modifications to the C-20 side chain of the macrolide ring. Compounds 7-12 exhibited a range of in vitro activities against HCT-116 and MDA-MB-435 cell lines. Fijianolides 8 and 10 were shown to disrupt interphase and mitotic division, but were less potent than 2. An in vivo evaluation of 2 using tumor-bearing severe combined immuno-deficiency mice demonstrated significant inhibition of growth in HCT-116 tumors over 28 days.

Publication types

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

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / isolation & purification*
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Drug Screening Assays, Antitumor
  • Humans
  • Macrolides / chemistry
  • Macrolides / isolation & purification*
  • Macrolides / pharmacology
  • Mice
  • Mice, SCID
  • Models, Molecular
  • Neoplasm Transplantation
  • Porifera / chemistry*
  • Structure-Activity Relationship
  • Taxoids / chemistry
  • Taxoids / isolation & purification*
  • Taxoids / pharmacology
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Macrolides
  • Taxoids
  • isolaulimalide
  • laulimalide