Synthesis, modification and docking studies of 5-sulfonyl isatin derivatives as SARS-CoV 3C-like protease inhibitors

College of Sciences, Tianjin University of Science and Technology, Tianjin 300457, China. Electronic address: .
Bioorganic & medicinal chemistry (Impact Factor: 2.79). 11/2013; 22(1). DOI: 10.1016/j.bmc.2013.11.028
Source: PubMed


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=1.04μM). These results indicated that these inhibitors could be potentially developed into anti-SARS drugs.

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