Sponge-Derived Fijianolide Polyketide Class: Further Evaluation of Their Structural and Cytotoxicity Properties

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• 作者：Tyler A. Johnson ; Karen Tenney ; Robert H. Cichewicz ; Brandon I. Morinaka ; Kimberly N. White ; Taro Amagata ; Balanehru Subramanian ; Joseph Media ; Susan L. Mooberry ; Frederick A. Valeriote ; Phillip Crews
• 刊名：Journal of Medicinal Chemistry
• 出版年：2007
• 出版时间：August 9, 2007
• 年：2007
• 卷：50
• 期：16
• 页码：3795 - 3803
• 全文大小：244K
• 年卷期：v.50,no.16(August 9, 2007)
• ISSN：1520-4804

文摘

The sponge-derived polyketide macrolides fijianolides A (<B>1) and B (2), isolaulimalide and laulimalide, havetaxol-like microtubule-stabilizing activity, and the latter exhibits potent cytotoxicity. Insight on thebiogeographical and phenotypic variations of Cacospongia mycofijiensis is presented that will enable afuture 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 themacrolide 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 lesspotent than 2. An in vivo evaluation of 2 using tumor-bearing severe combined immuno-deficiency micedemonstrated significant inhibition of growth in HCT-116 tumors over 28 days.