title: 1,2-benzisothiazol-3-one derivatives as a novel class of small-molecule caspase-3 inhibitors.
abstract: A novel series of 1,2-benzisothiazol-3-one derivatives was synthesized and their biological activities were evaluated for inhibiting caspase-3 and -7 activities, in which some of them showed low nanomolar potency against caspase-3 in vitro and significant protection against apoptosis in a camptothecin-induced Jurkat T cells system. Among the tested compounds, compound 5i exhibited the most potent caspase-3 inhibitory activity (IC50=1.15 nM). The molecular docking predicted the interactions and binding modes of the synthesized inhibitor in the caspase-3 active site.
authors.affiliation: College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wu
authors.affiliation: College of Life Science, NanKai University, Tianjin 300071, China.
authors.forename: Meiqi
authors.initials: M
authors.lastname: Lu
authors.affiliation: College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Zhihui
authors.initials: Z
authors.lastname: Yan
authors.affiliation: College of Biotechnology, Tianjin University of Science and Technology, Tianjin 300457, China.
authors.forename: Xiaobin
authors.initials: X
authors.lastname: Tang
authors.affiliation: High Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biotechnology and Medicine, TEDA, Tianjin 300457, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: College of Science, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address: liuwei2006@tust.edu.cn.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: College of Pharmacy, NanKai University, Tianjin 300071, China.
authors.forename: Honggang
authors.initials: H
authors.lastname: Zhou
authors.affiliation: College of Pharmacy, NanKai University, Tianjin 300071, China; High Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biotechnology and Medicine, TEDA, Tianjin 300457, China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Yang
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D052160:Benzothiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001665:Binding Sites; D002166:Camptothecin / Q000633:toxicity; D053148:Caspase 3 / Q000737:chemistry* / Q000378:metabolism; D061945:Caspase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D020134:Catalytic Domain; D006801:Humans; D019169:Jurkat Cells; D062105:Molecular Docking Simulation; D009025:Morpholines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D055672:Static Electricity; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D052160:Benzothiazoles; D061945:Caspase Inhibitors; D009025:Morpholines; C000593358:N-(4-morpholinophenyl)-3-oxobenzo(d)isothiazole-2(3H)-carboxamide; D013844:Thiazoles; D053148:Caspase 3; C015699:1,2-benzisothiazoline-3-one; D002166:Camptothecin
keywords: 1,2-Benzisothiazol-3-one; Apoptosis; Caspase-3; Inhibitors