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

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 tha...

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Bibliographic Details
Published in:Journal of medicinal chemistry 2007-08, Vol.50 (16), p.3795-3803
Main Authors: Johnson, Tyler A, Tenney, Karen, Cichewicz, Robert H, Morinaka, Brandon I, White, Kimberly N, Amagata, Taro, Subramanian, Balanehru, Media, Joseph, Mooberry, Susan L, Valeriote, Frederick A, Crews, Phillip
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - chemistry
Antineoplastic Agents - isolation & purification
Antineoplastic Agents - pharmacology
Biological and medical sciences
Cacospongia
Cell Line, Tumor
Drug Screening Assays, Antitumor
General pharmacology
Humans
Macrolides - chemistry
Macrolides - isolation & purification
Macrolides - pharmacology
Medical sciences
Mice
Mice, SCID
Models, Molecular
Neoplasm Transplantation
Pharmacognosy. Homeopathy. Health food
Pharmacology. Drug treatments
Porifera - chemistry
Structure-Activity Relationship
Taxoids - chemistry
Taxoids - isolation & purification
Taxoids - pharmacology
Transplantation, Heterologous
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Summary: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.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm070410z