Discovery of a new class of histone deacetylase inhibitors with a novel zinc binding group.

ABSTRACT: Small molecules featuring a hydroxamic acid or a benzamide zinc binding group (ZBG) are the most thoroughly studied histone deacetylase (HDAC) inhibitors. However, concerns about the pharmacokinetic liabilities of the hydroxamic acid moiety and potential metabolic toxicity of the aniline portion of benzamide HDAC inhibitors have stimulated research efforts aimed at discovering alternative ZBGs. Here we report the 2-(oxazol-2-yl)phenol moiety as a novel ZBG that can be used to produce compounds that are potent HDAC inhibitors. A series of analogues with this novel ZBG have been synthesized, and these analogues exhibit selective inhibition against HDAC1 as well as the class IIb HDACs (HDAC6 and HDAC10). Compound 10 possesses an IC₅₀ value of 7.5 μM in the MV-4-11 leukemia c

SUBMITTER: Li Y 

PROVIDER: S-EPMC4440699 | biostudies-literature | 2015 Apr

REPOSITORIES: biostudies-literature