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

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.

journal_name

J Med Chem

journal_title

Journal of medicinal chemistry

authors

Johnson TA,Tenney K,Cichewicz RH,Morinaka BI,White KN,Amagata T,Subramanian B,Media J,Mooberry SL,Valeriote FA,Crews P

doi

10.1021/jm070410z

subject

Has Abstract

pub_date

2007-08-09 00:00:00

pages

3795-803

issue

16

eissn

0022-2623

issn

1520-4804

journal_volume

50

pub_type

杂志文章

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