标题：PXD101 analogs with L-phenylglycine-containing branched cap as histone deacetylase inhibitors
作者：Li, Jingyao; Li, Xiaoyang; Wang, Xue; Hou, Jinning; Zang, Jie; Gao, Shuai; Xu, Wenfang; Zhang, Yingjie
作者机构：[Li, Jingyao; Li, Xiaoyang; Wang, Xue; Hou, Jinning; Zang, Jie; Gao, Shuai; Xu, Wenfang; Zhang, Yingjie] Shandong Univ, Dept Med Chem, Sch Pharmaceut 更多
通讯作者地址：[Zhang, YJ]Shandong Univ, Dept Med Chem, Sch Pharmaceut Sci, Jinan, Shandong, Peoples R China.
来源：CHEMICAL BIOLOGY & DRUG DESIGN
关键词：antiproliferative activity; HDAC inhibitory activity; HDAC isoform; selectivity; HDACs; inhibitor
摘要：Histone deacetylases (HDACs) allow histones to wrap DNA more tightly and finally lead to the repression of some tumor suppressor genes. Histone deacetylase inhibitors (HDACIs) have been proved to have effects on tumorigenesis and tumor progression. In this study, we reported the design, synthesis, and in vitro activity evaluation of novel PXD101 analogs with L-phenylglycine-containing cap as HDACIs. Our results showed that HDACs inhibitory activities of compounds 10k, 10r, and 10s were not only superior to the first approved HDACI SAHA, but also comparable to their parent compound PXD101, a recently approved HDACI in 2014. However, all 6 selected PXD101 analogs exhibited moderate in vitro antiproliferative activities, less potent than PXD101 and SAHA. Representative compound 10s showed similar HDACs isoform selective profile to PXD101, which demonstrated that introduction of L-phenylglycine-containing branched cap group could not change the isoform selectivity of PXD101 dramatically.