title: Design, synthesis and evaluation of 1,2-benzisothiazol-3-one derivatives as potent caspase-3 inhibitors.
abstract: A number of 1,2-benzisothiazol-3-one derivatives were prepared through structural modification of the original compound from high-throughput screening. Some analogues (e.g., 6b, 6r, 6s and 6w) were identified as novel and potent caspase inhibitors with IC50 of nanomolar. Structure-activity relationship (SAR) studies for caspase-3 inhibition were evaluated in vitro. Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. The present small molecule caspase-3 inhibitor with novel structures different from structures of known caspase inhibitors revealed a new direction for therapeutic strategies directed against diseases involving abnormally up-regulated apoptosis.
authors: College of Life Sciences, NanKai University, Tianjin 300071, China.
authors: Dazhi
authors: D
authors: Liu
authors: Zhen
authors: Z
authors: Tian
authors: Zhihui
authors: Z
authors: Yan
authors: Lixin
authors: L
authors: Wu
authors: Yan
authors: Y
authors: Ma
authors: Quan
authors: Q
authors: Wang
authors: Wei
authors: W
authors: Liu
authors: Honggang
authors: H
authors: Zhou
authors: Cheng
authors: C
authors: Yang
mesh_terms: D053148:Caspase 3 / Q000737:chemistry*; D061945:Caspase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D015195:Drug Design; D057075:Enzyme Assays; D057166:High-Throughput Screening Assays; D006801:Humans; D062105:Molecular Docking Simulation; D011994:Recombinant Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000737:chemistry
chemical_list: D061945:Caspase Inhibitors; D011994:Recombinant Proteins; D013844:Thiazoles; D053148:Caspase 3; C015699:1,2-benzisothiazoline-3-one