title: Improved antiproliferative activity of 1,3,4-thiadiazole-containing histone deacetylase (HDAC) inhibitors by introduction of the heteroaromatic surface recognition motif.
abstract: A series of 1,3,4-thiadiazole-containing hydroxamic acids, in accord with the common pharmacophore of histone deacetylase (HDAC) inhibitors (a Zn(2+) binding moiety-a linker-a surface recognition motif), was identified as submicromolar HDAC inhibitors by our group. In this study, we continued our efforts to develop 1,3,4-thiadiazole bearing hydroxamate analogues by modifying the surface recognition motif. We found that 1,3,4-thiadiazoles having a heteroaromatic substituent showed better HDAC inhibitory activity in enzymatic assay and higher antiproliferative potency in cellular assay compared to SAHA.
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Peng
authors.initials: P
authors.lastname: Guan
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Jinan, 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, Jinan, 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, Jinan, Shandong 250012, PR China.
authors.forename: Yichao
authors.initials: Y
authors.lastname: Wan
authors.affiliation: Department of Medicinal Chemistry, Key Laboratory of Chemical Biology (Ministry of Education), School of Pharmacy, Shandong University, Jinan, Shandong 250012, PR China.
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
authors.affiliation: Division of Pharmaceutical Sciences, School of Pharmacy, University of Wisconsin, 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, Jinan, Shandong 250012, PR China. Electronic address: haofangcn@sdu.edu.cn.
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
mesh_terms: D020816:Amino Acid Motifs; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D015195:Drug Design; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry; D062105:Molecular Docking Simulation; D017434:Protein Structure, Tertiary; D013329:Structure-Activity Relationship; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D013830:Thiadiazoles; C058949:1,3,4-thiadiazole; D006655:Histone Deacetylases
keywords: 1,3,4-Thiadiazole; Antiproliferation; Histone deacetylase inhibitor; Hydroxamic acid; Surface recognition motif