New approach towards the synthesis of selenosemicarbazones, useful compounds for Chagas' disease

Eur J Med Chem. 2016 Feb 15:109:107-13. doi: 10.1016/j.ejmech.2015.12.040. Epub 2015 Dec 23.

Abstract

Herein, we describe a new approach towards the synthesis of selenosemicarbazones. The reaction involves an O-Se exchange of semicarbazones using Ishihara reagent. Eleven selenosemicarbazones were prepared using this methodology, with low to moderate yields. Among the prepared compounds the m-bromo phenyl methyl derivative 1b was selected to be evaluated in vivo, in a murine model of acute Chagas' disease. Compound 1b 10 mg/kg bw/day reduced 50% of parasitaemia profile compared with the control group, but was less effective than Benznidazole (50 mg/kg bw/day reduced 90%) and toxic. These studies are important to guide future Chagas drug design.

Keywords: Chagas' disease; Iminochloride; Ishihara reagent; Selenosemicarbazone.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Animals
  • Chagas Disease / drug therapy*
  • Chemistry Techniques, Synthetic
  • Drug Design
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Organoselenium Compounds / chemical synthesis*
  • Organoselenium Compounds / chemistry
  • Organoselenium Compounds / therapeutic use*
  • Semicarbazones / chemical synthesis*
  • Semicarbazones / chemistry
  • Semicarbazones / therapeutic use*
  • Trypanocidal Agents / chemical synthesis*
  • Trypanocidal Agents / chemistry
  • Trypanocidal Agents / therapeutic use*
  • Trypanosoma cruzi / drug effects

Substances

  • Organoselenium Compounds
  • Semicarbazones
  • Trypanocidal Agents