Design, Synthesis, and Biological Evaluation of 2,4-Imidazolinedione Derivatives as HDAC6 Isoform-Selective Inhibitors.

ABSTRACT: Histone deacetylase 6 (HDAC6) has emerged as a promising drug target for various human diseases, including diverse neurodegenerative diseases and cancer. Herein, we reported a series of 2,4-imidazolinedione derivatives as novel HDAC6 isoform-selective inhibitors based on structure-based drug design. Most target compounds exhibit good profiles in a preliminary screening concerning HDAC6 inhibitory activities. Moreover, the most active compound 10c increases the acetylation level of α-tubulin with little effect on the acetylation of histone H3. Further biological evaluation suggested that potent compound 10c, which possesses good antiproliferative activity, could induce apoptosis in HL-60 cell by activating caspase 3.

SUBMITTER: Liang T 

PROVIDER: S-EPMC6691477 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature