title: Discovery of Multi-target Anticancer Agents Based on HDAC Inhibitor MS-275 and 5-FU.
abstract: 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.
authors.forename: Yuqi
authors.initials: Y
authors.lastname: Jiang
authors.forename: Xiaoguang
authors.initials: X
authors.lastname: Li
authors.forename: Xiaoyang
authors.initials: X
authors.lastname: Li
authors.forename: Jinning
authors.initials: J
authors.lastname: Hou
authors.forename: Yongzheng
authors.initials: Y
authors.lastname: Ding
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, 250012 Ji'nan, Shandong, PR China. wenfxu@163.com.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
authors.affiliation: Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Wenhua Road, 250012 Ji'nan, Shandong, PR China. zhangyingjie@sdu.edu.cn.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005472:Fluorouracil / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D011725:Pyridines / Q000494:pharmacology
chemical_list: C000614150:(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl) methyl-(4-((2-aminophenyl)carbamoyl)phenyl)carbamate; C000614149:(5-fluoro-2,4-dioxo-3,4-dihydropyrimidin-1(2H)-yl)methyl-4-((2-aminophenyl)carbamoyl)benzylcarbamate; D000970:Antineoplastic Agents; D001549:Benzamides; D056572:Histone Deacetylase Inhibitors; D011725:Pyridines; C118739:entinostat; D005472:Fluorouracil