4-nitroacetophenone-derived thiosemicarbazones and their copper(II) complexes with significant in vitro anti-trypanosomal activity

Eur J Med Chem. 2008 May;43(5):939-48. doi: 10.1016/j.ejmech.2007.06.020. Epub 2007 Jul 10.

Abstract

N(4)-methyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4M, 1), N(4),N(4)-dimethyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4DM, 2) and N(4)-piperidyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4Pip, 3) and their copper(II) complexes [Cu(4NO(2)Ac4M)(2)] (4), [Cu(4NO(2)Ac4DM)(2)] (5) and [Cu(4NO(2)Ac4Pip)(2)] (6) were tested for their in vitro ability to inhibit the growth of Trypanosoma cruzi epimastigote forms. H4NO(2)Ac4DM (2), [Cu(4NO(2)Ac4M)(2)] (4) and [Cu(4NO(2)Ac4DM)(2)] (5) proved to be as active as the clinical reference drugs nifurtimox and benznidazol. Taking into consideration the serious side effects and the poor efficacy of the reference drugs, as well as the appearance of resistance during treatment, the studied compounds could constitute a new class of anti-trypanosomal drug candidates.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetophenones / chemical synthesis*
  • Acetophenones / chemistry
  • Acetophenones / pharmacology
  • Animals
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / chemistry
  • Copper*
  • Crystallography, X-Ray
  • Electrochemistry
  • Electron Spin Resonance Spectroscopy
  • Humans
  • In Vitro Techniques
  • Macrophages / drug effects
  • Macrophages / parasitology
  • Magnetic Resonance Spectroscopy
  • Molecular Structure
  • Thiosemicarbazones / chemical synthesis*
  • Thiosemicarbazones / chemistry
  • Thiosemicarbazones / pharmacology
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / pharmacology
  • Trypanosoma cruzi / drug effects

Substances

  • Acetophenones
  • Chelating Agents
  • Thiosemicarbazones
  • Trypanocidal Agents
  • Copper