N-benzylisatin Sulfonamide Analogues as Potent caspase-3 Inhibitors: Synthesis, in Vitro Activity, and Molecular Modeling Studies

J Med Chem. 2005 Dec 1;48(24):7637-47. doi: 10.1021/jm0506625.


A number of isatin sulfonamide analogues were prepared and their potencies for inhibiting caspase-1, -3, -6, -7, and -8 were evaluated in vitro. Several compounds displaying a nanomolar potency for inhibiting the executioner caspases, caspase-3 and caspase-7, were identified. These compounds were also observed to have a low potency for inhibiting the initiator caspases, caspase-1 and caspase-8, and caspase-6. Molecular modeling studies provided further insight into the interaction of this class of compounds with activated caspase-3. The results of the current study revealed a number of non-peptide-based caspase inhibitors that may be useful in assessing the role of inhibiting the executioner caspases in minimizing tissue damage in disease conditions characterized by unregulated apoptosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Apoptosis
  • Benzyl Compounds / chemical synthesis*
  • Benzyl Compounds / chemistry
  • Caspase 3
  • Caspase Inhibitors*
  • Caspases / chemistry*
  • Isatin / analogs & derivatives*
  • Isatin / chemical synthesis*
  • Isatin / chemistry
  • Models, Molecular
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry


  • Benzyl Compounds
  • Caspase Inhibitors
  • Sulfonamides
  • Isatin
  • Caspase 3
  • Caspases