Synthesis and evaluation of isatin analogs as caspase-3 inhibitors: introduction of a hydrophilic group increases potency in a whole cell assay

Bioorg Med Chem Lett. 2011 Apr 15;21(8):2192-7. doi: 10.1016/j.bmcl.2011.03.015.

Abstract

A series of isatin analogs containing a hydrophilic group, including a pyridine ring, ethylene glycol group, and a triazole ring, have been synthesized, and their inhibition potency for caspase-3 was measured both in vitro (i.e., recombinant enzyme) and in whole cells (HeLa cells). The analogs having a hydrophilic group, including 12, 13, 16, 38, and 40, have dramatically increased activity in vitro and in HeLa cells compared to the corresponding unsubstituted N-phenyl isatin analogs.

Publication types

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

MeSH terms

  • Caspase 3 / genetics
  • Caspase 3 / metabolism
  • Caspase Inhibitors*
  • HeLa Cells
  • Humans
  • Hydrophobic and Hydrophilic Interactions
  • Isatin / analogs & derivatives*
  • Isatin / chemical synthesis
  • Isatin / pharmacology
  • Protease Inhibitors / chemical synthesis
  • Protease Inhibitors / chemistry*
  • Protease Inhibitors / pharmacology
  • Recombinant Proteins / chemistry
  • Recombinant Proteins / genetics
  • Recombinant Proteins / metabolism
  • Structure-Activity Relationship
  • Triazoles / chemistry

Substances

  • Caspase Inhibitors
  • Protease Inhibitors
  • Recombinant Proteins
  • Triazoles
  • Isatin
  • Caspase 3