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

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

Research output: Contribution to journalArticle

46 Scopus citations

Abstract

The sponge-derived polyketide macrolides frjianolides 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 frjianolides. In addition to frjianolides 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.

Original languageEnglish (US)
Pages (from-to)3795-3803
Number of pages9
JournalJournal of Medicinal Chemistry
Volume50
Issue number16
DOIs
StatePublished - Aug 9 2007

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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    Johnson, T. A., Tenney, K., Cichewicz, R. H., Morinaka, B. I., White, K. N., Amagata, T., Subramanian, B., Media, J., Mooberry, S. L., Valeriote, F. A., & Crews, P. (2007). Sponge-derived fijianolide polyketide class: Further evaluation of their structural and cytotoxicity properties. Journal of Medicinal Chemistry, 50(16), 3795-3803. https://doi.org/10.1021/jm070410z