Title

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

Department

Natural Sciences and Mathematics

Document Type

Article

Source

Journal of Medicinal Chemistry

Publication Date

11-27-2008

ISSN

1520-4804

Volume

51

Issue

22

First Page

7234

Last Page

7242

Digital Object Identifier / DOI

https://doi.org/10.1021/jm8008585

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 microM. Among the cytotoxic derivatives, compound 9 did not exhibit microfilament-disrupting activity at 5 microM. The implications of this observation and the value of further therapeutic study on key latrunculin derivatives are discussed.

PubMed ID

18942825

Rights

Copyright © 2008 American Chemical Society

Publisher's Statement

This document is the Accepted Manuscript version of a Published Work that appeared in final form in the Journal of Medicinal Chemistry, copyright © American Chemical Society after peer review and technical editing by the publisher.

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