文献类型：期刊文献

英文题名：Design and Synthesis of Novel Urushiol Derivatives as Potent Histone Deacetylase Inhibitors and Evaluation of Their Biological Properties

作者：Zhou, Hao[1,2] Qi, Zhiwen[1,2] Liu, Danyang[1,2] Xue, Xingyin[1,2] Wang, Chengzhang[1,2]

第一作者：Zhou, Hao;周昊

机构：[1] Institute of Chemical Industry of Forest Products, Chinese Academy of Forestry, Nanjing, 210042, China; [2] Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University, Nanjing, 210037, China

年份：2023

外文期刊名：SSRN

收录：EI(收录号：20230085885)

语种：英文

外文关键词：Cell culture - Cell death - Electrophoresis

摘要：Herein, a novel series of eleven urushiol-based hydroxamic acid HDAC inhibitors were designed, synthesized, and biologically evaluated. Compounds 1-11 exhibited potent inhibitory activities against HDAC8 with IC50 of 16.11 ~ 41.15 nM, and against HDAC1/2 with IC50 of 50.19 ~ 240.17 nM in vitro, while showed negligible inhibition against HDAC6 (>1409.59 nM), indicating their privileged structure acceptable targeting class I HDACs. Accordingly, six compounds showed superior in vitro anti-proliferative activity against four human cancer cell lines (A2780, HT-29, MDA-MB-231, HepG2 with IC50= 2.31~5.13 μM). In addition, representative compounds 2 and 11 bound tightly to the active site of HDAC8, administration of them also led to MDA-MB-231 cells remarkable apoptosis and cell cycle arrest in the G2/M phase. Besides, Western blot analysis validated those compounds 2 and 11 caused a noticeable enhancement in the acetylation of only histone H3 but not α-tubulin, indicating them two were selective class I HDACs inhibitors. ? 2023, The Authors. All rights reserved.