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Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity.

ABSTRACT: 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 substituents 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.

SUBMITTER: Medda F

PROVIDER: S-EPMC2691587 | biostudies-literature | 2009 May

REPOSITORIES: biostudies-literature

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Novel cambinol analogs as sirtuin inhibitors: synthesis, biological evaluation, and rationalization of activity.

Medda Federico F Russell Rupert J M RJ Higgins Maureen M McCarthy Anna R AR Campbell Johanna J Slawin Alexandra M Z AM Lane David P DP Lain Sonia S Westwood Nicholas J NJ

Journal of medicinal chemistry 20090501 9

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 substituents 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 analo ...[more]

PMID: 19419202

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