标题：Design, Synthesis, and Biological Evaluation of 2,4-Imidazolinedione Derivatives as HDAC6 Isoform-Selective Inhibitors
作者：Liang, Tao; Hou, Xuben; Zhou, Yi; Yang, Xinying; Fang, Hao
作者机构：[Liang, Tao; Hou, Xuben; Zhou, Yi; Yang, Xinying; Fang, Hao] Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 Wenhu 更多
通讯作者地址：[Fang, H]Shandong Univ, Sch Pharmaceut Sci, Minist Educ, Dept Med Chem,Key Lab Chem Biol, 44 Wenhuaxi Rd, Jinan 250012, Shandong, Peoples R China.
来源：ACS MEDICINAL CHEMISTRY LETTERS
关键词：HDAC6; isoform-selective; 2,4-imidazolinedione; antiproliferative;; apoptosis
摘要：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 alpha-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.