Document Type

Article

Publication Date

10-4-2008

Publication Title

Journal of Enzyme Inhibition and Medicinal Chemistry

Abstract

Butyric acid and trichostatin A (TSA) are anti-cancer compounds that cause the upregulation of genes involved in differentiation and cell cycle regulation by inhibiting histone deacetylase (HDAC) activity. In this study we have synthesized and evaluated compounds that combine the bioavailability of short-chain fatty acids, like butyric acid, with the bidentate binding ability of TSA. A series of analogs were made to examine the effects of chain length, simple aromatic cap groups, and substituted hydroxamates on the compounds' ability to inhibit rat-liver HDAC using a fluorometric assay. In keeping with previous structure-activity relationships, the most effective inhibitors consisted of longer chains and hydroxamic acid groups. It was found that 5-phenylvaleric hydroxamic acid and 4-benzoylbutyric hydroxamic acid were the most potent inhibitors with IC50's of 5 microM and 133 microM respectively.

Volume

23

Issue

4

First Page

549

Last Page

555

DOI

https://doi.org/10.1080/14756360701715703

ISSN

1475-6366

Comments

ESSN: 1475-6374

Rights

Taylor & Francis

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