Open AccessDesign, Synthesis, and Biological Evaluation of 2,4-Imidazolinedione Derivatives as HDAC6 Isoform-Selective Inhibitors
Author(s) -
Liang Tao,
Xuben Hou,
Yi Zhou,
Yang Xia,
Hao Fang
Publication year - 2019
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.9b00084
Subject(s) - hdac6 , acetylation , gene isoform , histone deacetylase , histone , chemistry , biochemistry , hdac1 , apoptosis , computational biology , pharmacology , cancer research , biology , gene
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.