Synthesis and evaluation of isatin derivatives as effective SARS coronavirus 3CL protease inhibitors

Bioorg Med Chem Lett. 2005 Jun 15;15(12):3058-62. doi: 10.1016/j.bmcl.2005.04.027.

Abstract

N-Substituted isatin derivatives were prepared from the reaction of isatin and various bromides via two steps. Bioactivity assay results (in vitro tests) demonstrated that some of these compounds are potent and selective inhibitors against SARS coronavirus 3CL protease with IC50 values ranging from 0.95 to 17.50 microM. Additionally, isatin 4o exhibited more potent inhibition for SARS coronavirus protease than for other proteases including papain, chymotrypsin, and trypsin.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Chymotrypsin / pharmacology
  • Computer Simulation
  • Coronavirus 3C Proteases
  • Cysteine Endopeptidases
  • Endopeptidases
  • Enzyme Activation
  • Fluorescence Resonance Energy Transfer
  • Humans
  • Isatin / analogs & derivatives*
  • Isatin / chemical synthesis
  • Isatin / pharmacology*
  • Molecular Structure
  • Papain / pharmacology
  • Protease Inhibitors / chemical synthesis*
  • Protease Inhibitors / chemistry
  • Protease Inhibitors / pharmacology*
  • Severe acute respiratory syndrome-related coronavirus / enzymology*
  • Structure-Activity Relationship
  • Substrate Specificity
  • Trypsin / pharmacology
  • Viral Proteins / antagonists & inhibitors*

Substances

  • Protease Inhibitors
  • Viral Proteins
  • Isatin
  • Endopeptidases
  • Chymotrypsin
  • Trypsin
  • Cysteine Endopeptidases
  • Papain
  • Coronavirus 3C Proteases