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 journalArticlepeer-review

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.

Original languageAmerican English
Pages (from-to)3795-3803
Number of pages9
JournalJournal of Medicinal Chemistry
Volume50
Issue number16
DOIs
StatePublished - Jul 10 2007
Externally publishedYes

Funding

FundersFunder number
National Cancer InstituteR01CA047135

    Keywords

    • Animals
    • Antineoplastic Agents
    • Cell Line
    • Tumor
    • Drug Screening Assays
    • Antitumor
    • Humans
    • Macrolides
    • Mice
    • SCID
    • Models
    • Molecular
    • Neoplasm Transplantation
    • Porifera
    • Structure-Activity Relationship
    • Taxoids
    • Transplantation
    • Heterologous

    Disciplines

    • Biochemistry
    • Natural Products Chemistry and Pharmacognosy

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