文章基本信息

标题：Syntheses and Biological Evaluation of Novel Hydroxamic Acid Derivatives Containing Purine Moiety as Histone Deacetylase Inhibitors
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作者：Zhaoxing Xu ; Yongchao Yang ; Xi Mai 等
期刊名称：Chemical and Pharmaceutical Bulletin
印刷版ISSN：0009-2363
电子版ISSN：1347-5223
出版年度：2018
卷号：66
期号：4
页码：439-451
DOI：10.1248/cpb.c17-00997
语种：English
出版社：The Pharmaceutical Society of Japan
摘要：The novel hydroxamates containing purine scaffold were designed, synthesized and screened for their biological activities as histone deacetylase (HDAC) inhibitors. Some of them exhibited excellent acti-HDACs activities and antiproliferative activities, the most promising compound was 7m′ . Western blot analysis indicated the compounds 7f′ , 7l′ , 7m′ , 7o′ could increase histone H3 acetylation levels in HCT116 and K562 cell lines, and 7m′ increased the level of acetyl histone H3 in a dose-dependent manner, which is similar to the behavior of suberoylanilide hydroxamic acid ( SAHA ). Molecular docking study revealed that the conformation of 7m′ in the active site of HDAC2 was similar to positive drug SAHA , which were oriented with the hydroxamic acid towards the catalytic center and formed metal binding with zinc ion.
关键词：hydroxamic acid;purine;histone deacetylase;antiproliferative;Western blot analysis