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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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