title: Design, synthesis, and biological evaluation of novel histone deacetylase 1 inhibitors through click chemistry.
abstract: We report the design, synthesis, and biological evaluation of a new series of HDAC1 inhibitors using click chemistry. Compound 17 bearing a phenyl ring at meta-position was identified to show much better selectivity for HDAC1 over HDAC7 than SAHA. The compond 17 also showed better in vitro anticancer activities against several cancer cell lines than that of SAHA. This work could serve as a foundation for further exploration of selective HDAC inhibitors using the compound 17 molecular scaffold.
authors.affiliation: Laboratory of Medicinal Chemistry, Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences, Guangzhou 510530, PR China.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Sun
authors.forename: Yiwu
authors.initials: Y
authors.lastname: Yao
authors.forename: Chunping
authors.initials: C
authors.lastname: Liu
authors.forename: Hua
authors.initials: H
authors.lastname: Li
authors.forename: Hequan
authors.initials: H
authors.lastname: Yao
authors.forename: Xiaowen
authors.initials: X
authors.lastname: Xue
authors.forename: Jinsong
authors.initials: J
authors.lastname: Liu
authors.forename: Zhengchao
authors.initials: Z
authors.lastname: Tu
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry; D001665:Binding Sites; D020134:Catalytic Domain; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D057930:Click Chemistry; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004354:Drug Screening Assays, Antitumor; D056284:Histone Deacetylase 1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000378:metabolism / Q000633:toxicity; D006655:Histone Deacetylases / Q000737:chemistry / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D006877:Hydroxamic Acids / Q000737:chemistry / Q000378:metabolism / Q000633:toxicity; D062105:Molecular Docking Simulation; D011485:Protein Binding; D013329:Structure-Activity Relationship; D000077337:Vorinostat
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D000077337:Vorinostat; C543273:HDAC7 protein, human; D056284:Histone Deacetylase 1; D006655:Histone Deacetylases