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
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.