Novel Cambinol Analogs as Sirtuin Inhibitors: Synthesis, Biological Evaluation, and Rationalization of Activity

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• 作者：Federico Medda ; Rupert J. M. Russell ; Maureen Higgins ; Anna R. McCarthy ; Johanna Campbell ; Alexandra M. Z. Slawin ; David P. Lane ; Sonia Lain ; Nicholas J. Westwood
• 刊名：Journal of Medicinal Chemistry
• 出版年：2009
• 出版时间：May 14, 2009
• 年：2009
• 卷：52
• 期：9
• 页码：2673-2682
• 全文大小：221K
• 年卷期：v.52,no.9(May 14, 2009)
• ISSN：1520-4804

文摘

The tenovins and cambinol are two classes of sirtuin inhibitor that exhibit antitumor activity in preclinical models. This report describes modifications to the core structure of cambinol, in particular by incorporation of substitutents at the N1-position, which lead to increased potency and modified selectivity. These improvements have been rationalized using molecular modeling techniques. The expected functional selectivity in cells was also observed for both a SIRT1 and a SIRT2 selective analog.