标题：Discovery of Multi-target Anticancer Agents Based on HDAC Inhibitor MS-275 and 5-FU
作者：Jiang, Yuqi; Li, Xiaoguang; Li, Xiaoyang; Hou, Jinning; Ding, Yongzheng; Zhang, Jian; Xu, Wenfang; Zhang, Yingjie
作者机构：[Jiang, Yuqi; Li, Xiaoguang; Li, Xiaoyang; Hou, Jinning; Ding, Yongzheng; Zhang, Jian; Xu, Wenfang; Zhang, Yingjie] Shandong Univ, Sch Pharmaceut Sci, 更多
通讯作者：Xu, WF;Zhang, YJ
通讯作者地址：[Xu, WF; Zhang, YJ]Shandong Univ, Sch Pharmaceut Sci, Dept Med Chem, 44 West Wenhua Rd, Jinan 250012, Shandong, Peoples R China.
关键词：Anticancer; HDAC; MS-275; Multitarget; 5-Fluorouracil
摘要：Histone deacetylases (HDACs) inhibitors have multiple effects targeting the cancer cells and have become one of the promising cancer therapeutics with possibly broad applicability. Combination of HDAC inhibitors with the cytotoxic fluorouracil (5-FU) showed additive and synergistic effects both in vitro and in vivo. To explore the possibility in cancer therapy of a bivalent agent that combines two bioactive groups within a single molecular architecture, we designed and synthesized new dual-acting compounds by combining the bioactive fragment of MS-275, a clinical HDACs inhibitor, with cytotoxic agent 5-FU. The target compounds 9a and 9b showed comparable HDACs inhibition with MS-275 and moderate antiproliferative acitivities against six cancer cells lines.