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  3. Design and synthesis of novel histone deacetylase inhibitor derived from nuclear localization signal peptide

Design and synthesis of novel histone deacetylase inhibitor derived from nuclear localization signal peptide

  • Bioorg Med Chem Lett. 2009 Dec 1;19(23):6588-90. doi: 10.1016/j.bmcl.2009.10.028.
Joshua C Canzoneri 1,  Po C Chen,  Adegboyega K Oyelere
Affiliations

Affiliation

  • 1 School of Chemistry and Biochemistry, Parker H Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, Atlanta, GA 30332-0400, USA.
PMID: 19854643 DOI: 10.1016/j.bmcl.2009.10.028
Abstract

We describe herein the synthesis and characterization of a new class of histone deacetylase (HDAC) inhibitors derived from conjugation of a suberoylanilide hydroxamic acid-like aliphatic-hydroxamate pharmacophore to a nuclear localization signal peptide. We found that these conjugates inhibited the histone deacetylase activities of HDACs 1, 2, 6, and 8 in a manner similar to suberoylanilide hydroxamic acid (SAHA). Notably, compound 7b showed a threefold improvement in HDAC 1/2 inhibition, a threefold increase in HDAC 6 selectivity and a twofold increase in HDAC 8 selectivity when compared to SAHA.

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