title: Synthesis, modification and docking studies of 5-sulfonyl isatin derivatives as SARS-CoV 3C-like protease inhibitors.
abstract: The Severe Acute Respiratory Syndrome (SARS) is a serious life-threatening and strikingly mortal respiratory illness caused by SARS-CoV. SARS-CoV which contains a chymotrypsin-like main protease analogous to that of the main picornavirus protease, 3CL(pro). 3CL(pro) plays a pivotal role in the viral replication cycle and is a potential target for SARS inhibitor development. A series of isatin derivatives as possible SARS-CoV 3CL(pro) inhibitors was designed, synthesized, and evaluated by in vitro protease assay using fluorogenic substrate peptide, in which several showed potent inhibition against the 3CL(pro). Structure-activity relationship was analyzed, and possible binding interaction modes were proposed by molecular docking studies. Among all compounds, 8k₁ showed most potent inhibitory activity against 3CL(pro) (IC₅₀=1.04 μM). These results indicated that these inhibitors could be potentially developed into anti-SARS drugs.
authors: College of Sciences, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address: liuwei2006@tust.edu.cn.
authors: Wei
authors: W
authors: Liu
authors: College of Life Sciences, NanKai University, Tianjin 300071, China.
authors: He-Min
authors: HM
authors: Zhu
authors: High Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biotechnology and Medicine, TEDA, Tianjin 300457, China.
authors: Guo-Jun
authors: GJ
authors: Niu
authors: College of Life Sciences, NanKai University, Tianjin 300071, China.
authors: En-Zhi
authors: EZ
authors: Shi
authors: College of Pharmacy, NanKai University, Tianjin 300071, China.
authors: Jie
authors: J
authors: Chen
authors: High Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biotechnology and Medicine, TEDA, Tianjin 300457, China.
authors: Bo
authors: B
authors: Sun
authors: High Throughput Molecular Drug Discovery Center, Tianjin International Joint Academy of Biotechnology and Medicine, TEDA, Tianjin 300457, China.
authors: Wei-Qiang
authors: WQ
authors: Chen
authors: College of Pharmacy, NanKai University, Tianjin 300071, China.
authors: Hong-Gang
authors: HG
authors: Zhou
authors: 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: Cheng
authors: C
authors: Yang
mesh_terms: D006801:Humans; D007510:Isatin / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011480:Protease Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D045473:Severe acute respiratory syndrome-related coronavirus / Q000187:drug effects* / Q000378:metabolism; D013329:Structure-Activity Relationship
chemical_list: D011480:Protease Inhibitors; D007510:Isatin
keywords: Docking studies; Inhibitor; Isatin; SARS