Title

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

Department

Natural Sciences and Mathematics

Document Type

Article

Source

Journal of Medicinal Chemistry

Publication Date

8-9-2007

ISSN

0022-2623

Volume

50

Issue

16

First Page

3795

Last Page

3803

Digital Object Identifier / DOI

https://doi.org/10.1021/jm070410z

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.

PubMed ID

17622130

Rights

Copyright © 2007 American Chemical Society

Publisher's Statement

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher.

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