Hydroxyl Ketone-Based Histone Deacetylase Inhibitors To Gain Insight into Class I HDAC Selectivity versus That of HDAC6.

ABSTRACT: Little is known about the biological and structural features that govern the isoform selectivity for class I histone deacetylases (HDACs) over HDAC6. In addition to that for known inhibitors, like benzamides, psammaplin A, and cyclodepsipeptide-derived thiols, selectivity was also observed for naturally occurring cyclopeptide HDAC inhibitors with an aliphatic flexible linker and ketonelike zinc-binding group (ZBG). The present study reports that this isoform selectivity is mainly due to the linker and ZBG, as replacement of the cyclopeptide cap region by a simple aniline retained class I HDAC isoform selectivity toward HDAC6 in enzymatic assays. The best cyclopeptide-free analogues preserved efficacy against Plasmodium falciparum and cancer cell lines. Molecular modeling provided hy

SUBMITTER: Traore MDM 

PROVIDER: S-EPMC6044785 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature