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

Bioorg Med Chem. 2014 Jan 1;22(1):292-302. doi: 10.1016/j.bmc.2013.11.028. Epub 2013 Nov 21.


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.

Keywords: Docking studies; Inhibitor; Isatin; SARS.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Humans
  • Isatin / chemical synthesis*
  • Isatin / chemistry
  • Molecular Structure
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Severe acute respiratory syndrome-related coronavirus / drug effects*
  • Severe acute respiratory syndrome-related coronavirus / metabolism
  • Structure-Activity Relationship


  • Protease Inhibitors
  • Isatin