title: Design, synthesis and preliminary bioactivity evaluations of substituted quinoline hydroxamic acid derivatives as novel histone deacetylase (HDAC) inhibitors.
abstract: Inhibition of HDACs activity has become a promising therapeutic strategy in clinical practice to reverse the abnormal epigenetic states of cancer and other diseases. Therefore, HDAC inhibitors become a relatively new class of anti-cancer agent. In the present study, we reported the design and synthesis of a series of novel HDAC inhibitors using various substituted quinoline rings as the cap group. In vitro studies showed that some compounds have good inhibitory activities against HDACs and potent antiproliferative activities in some tumor cell lines. Especially, compound 9w (IC50=85 nM), exhibited better inhibitory effect compared with SAHA (IC50=161 nM).
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, PR China.
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, PR China.
authors.forename: Xuben
authors.initials: X
authors.lastname: Hou
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, PR China.
authors.forename: Huansheng
authors.initials: H
authors.lastname: Fu
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, PR China.
authors.forename: Xiaole
authors.initials: X
authors.lastname: Pan
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, PR China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
authors.affiliation: School of Pharmacy, University of Wisconsin, 777 Highland Avenue, Madison 53705, USA.
authors.forename: Weiping
authors.initials: W
authors.lastname: Tang
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Ji'nan, Shandong 250012, PR China. Electronic address: haofangcn@sdu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
mesh_terms: D001665:Binding Sites; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D011804:Quinolines / Q000737:chemistry; D013329:Structure-Activity Relationship
chemical_list: D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D011804:Quinolines; C037219:quinoline; D006655:Histone Deacetylases
keywords: Anti-proliferative; HDAC; Hydroxamic acid; Inhibitor; Quinoline