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:Fang, H
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
出版年:2019
卷:10
期:8
页码:1122-1127
DOI:10.1021/acsmedchemlett.9b00084
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.
收录类别:SCOPUS;SCIE
Scopus被引频次:2
资源类型:期刊论文
原文链接:https://www.scopus.com/inward/record.uri?eid=2-s2.0-85071133431&doi=10.1021%2facsmedchemlett.9b00084&partnerID=40&md5=ee8260609451b9b938898f6cbdc65fa4
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