title: Design, synthesis and preliminary activity assay of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as novel Histone deacetylases (HDACs) inhibitors.
abstract: Histone deacetylases (HDACs) are enzymes involved in tumor genesis and development. Herein, we report a novel series of 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid derivatives as HDACs inhibitors. The preliminary biological screening showed that most of our compounds exhibited potent inhibitory activity against HDACs. Within this series, five compounds, 13a (IC(50)=0.58+/-0.10 microM), 7d (IC(50)=1.00+/-0.16 microM), 8l (IC(50)=1.06+/-0.14 microM), 7i (IC(50)=1.17+/-0.19 microM) and 7a (IC(50)=1.29+/-0.15 microM) possessed better HDACs inhibitory activity than Vorinostat (IC(50)=1.48+/-0.20 microM). So these five compounds could be used as novel lead compounds for further design of HDACs inhibitors. The anti-proliferative activities of a few compounds and the structure-activity relationships are also briefly discussed.
authors.affiliation: Department of Medicinal Chemistry, School of Pharmacy, Shandong University, Ji'nan, Shandong, 250012, PR China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jinhong
authors.initials: J
authors.lastname: Feng
authors.forename: Chunxi
authors.initials: C
authors.lastname: Liu
authors.forename: Lei
authors.initials: L
authors.lastname: Zhang
authors.forename: Jie
authors.initials: J
authors.lastname: Jiao
authors.forename: Hao
authors.initials: H
authors.lastname: Fang
authors.forename: Li
authors.initials: L
authors.lastname: Su
authors.forename: Xiaopan
authors.initials: X
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Zhang
authors.forename: Minyong
authors.initials: M
authors.lastname: Li
authors.forename: Binghe
authors.initials: B
authors.lastname: Wang
authors.forename: Wenfang
authors.initials: W
authors.lastname: Xu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001665:Binding Sites; D020134:Catalytic Domain; D045744:Cell Line, Tumor; D003198:Computer Simulation; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D018922:HL-60 Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry* / Q000378:metabolism; D006801:Humans; D006877:Hydroxamic Acids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007546:Isoquinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D044005:Tetrahydroisoquinolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D006877:Hydroxamic Acids; D007546:Isoquinolines; D044005:Tetrahydroisoquinolines; C549968:benzyl 7-(2-(hydroxyamino)-2-oxoethoxy)-3-(phenethylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate; C549967:tert-butyl 7-(2-(hydroxyamino)-2-oxoethoxy)-3-(4-methoxyphenylcarbamoyl)-3,4-dihydroisoquinoline-2(1H)-carboxylate; C078986:1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid; D006655:Histone Deacetylases