Synthesis and in vitro evaluation of sulfonamide isatin Michael acceptors as small molecule inhibitors of caspase-6

J Med Chem. 2009 Apr 23;52(8):2188-91. doi: 10.1021/jm900135r.

Abstract

A key step in the onset of Huntington's disease is the caspase-6 mediated cleavage of the protein huntingtin into toxic fragments. Therefore, the inhibition of caspase-6 has been identified as a target for therapeutic drug development for the treatment of this disease. In this study, a series of isatin sulfonamide Michael acceptors having a high nanomolar potency for inhibiting caspase-6 and increased selectivity for caspase-6 versus caspase-3 inhibition is reported.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Caspase 3 / chemistry
  • Caspase 6 / chemistry
  • Caspase Inhibitors*
  • Humans
  • Isatin / analogs & derivatives*
  • Isatin / chemical synthesis*
  • Isatin / chemistry
  • Recombinant Proteins / antagonists & inhibitors
  • Recombinant Proteins / chemistry
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry

Substances

  • Caspase Inhibitors
  • Recombinant Proteins
  • Sulfonamides
  • Isatin
  • CASP6 protein, human
  • Caspase 3
  • Caspase 6