Interrogating the bioactive pharmacophore of the latrunculin chemotype by investigating the metabolites of two taxonomically unrelated sponges

Taro Amagata, Tyler A. Johnson, Robert H. Cichewicz, Karen Tenney, Susan L. Mooberry, Joseph Media, Matthew Edelstein, Frederick A. Valeriote, Phillip Crews

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

This study involved a campaign to isolate and study additional latrunculin analogues from two taxonomically unrelated sponges, Cacospongia mycofijiensis and Negombata magnifica. A total of 13 latrunculin analogues were obtained by four different ways, reisolation (1-4), our repository (5, 6), new derivatives (7-12), and a synthetic analogue (7a). The structures of the new metabolites were elucidated on the basis of a combination of comprehensive 1D and 2D NMR analysis, application of DFT calculations, and the preparation of acetonide derivative 7a. The cytotoxicities against both murine and human cancer cell lines observed for 1, 2, 7, 7a, 8, 9, and 12 were significant, and the IC 50 range was 0.5-10 μM. Among the cytotoxic derivatives, compound 9 did not exhibit microfilament-disrupting activity at 5 μM. The implications of this observation and the value of further therapeutic study on key latrunculin derivatives are discussed.

Original languageEnglish (US)
Pages (from-to)7234-7242
Number of pages9
JournalJournal of Medicinal Chemistry
Volume51
Issue number22
DOIs
StatePublished - Nov 27 2008

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ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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