Thiosemicarbazones derived from 1-indanones as new anti-Trypanosoma cruzi agents

Bioorg Med Chem. 2011 Nov 15;19(22):6818-26. doi: 10.1016/j.bmc.2011.09.037. Epub 2011 Sep 24.

Abstract

In the present work, we synthesized a series of thiosemicarbazones derived from 1-indanones with good anti-Trypanosoma cruzi activity. Most of them displayed remarkable trypanosomicidal activity. All the compounds showed nonspecific cytotoxicity on human erythrocytes. The ability of the new compounds to inhibit cruzipain, the major cysteine protease of T. cruzi, was also explored. Thiosemicarbazones 12 and 24 inhibited this enzyme at the dose assayed. This interaction was also studied in terms of molecular docking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cysteine Endopeptidases / metabolism
  • Cysteine Proteinase Inhibitors / chemistry*
  • Cysteine Proteinase Inhibitors / pharmacology
  • Erythrocytes / drug effects
  • Humans
  • Indans / chemistry*
  • Indans / pharmacology*
  • Models, Molecular
  • Molecular Conformation
  • Protozoan Proteins
  • Thiosemicarbazones / chemistry*
  • Thiosemicarbazones / pharmacology*
  • Trypanocidal Agents / chemistry*
  • Trypanocidal Agents / pharmacology
  • Trypanosoma cruzi / drug effects*
  • Trypanosoma cruzi / enzymology

Substances

  • Cysteine Proteinase Inhibitors
  • Indans
  • Protozoan Proteins
  • Thiosemicarbazones
  • Trypanocidal Agents
  • Cysteine Endopeptidases
  • cruzipain