title: Design, synthesis and preliminary bioactivity studies of 1,3,4-thiadiazole hydroxamic acid derivatives as novel histone deacetylase inhibitors.
abstract: Histone deacetylase (HDAC) inhibitors have emerged as a new class of anticancer agents, targeting the biological processes including cell cycle, apoptosis and differentiation. In the present study, a series of 1,3,4-thiadiazole based hydroxamic acids were developed as potent HDAC inhibitors. Some of them showed good inhibitory activity in HDAC enzyme assay and potent growth inhibition in some tumor cell lines. Among them, compound 6i (IC(50) = 0.089 μM), exhibited better inhibitory effect compared with SAHA (IC(50) = 0.15 μM).
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: Peng
authors.initials: P
authors.lastname: Guan
authors.forename: Feng'e
authors.initials: F
authors.lastname: Sun
authors.forename: Xuben
authors.initials: X
authors.lastname: Hou
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.forename: Fan
authors.initials: F
authors.lastname: Yi
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D020014:K562 Cells; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C576646:1,3,4-thiadiazole hydroxamic acid; D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013830:Thiadiazoles; D006655:Histone Deacetylases