Bioorganic & Medicinal Chemistry Letters 2009-01-01

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

Joshua C. Canzoneri, Po C. Chen, Adegboyega K. Oyelere

文献索引：Bioorg. Med. Chem. Lett. 19(23) , 6588-90, (2009)

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摘要

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.