2-Pyridyl thiazoles as novel anti-Trypanosoma cruzi agents: structural design, synthesis and pharmacological evaluation

  • Eur J Med Chem. 2014 Oct 30:86:48-59. doi: 10.1016/j.ejmech.2014.08.012.
Marcos Veríssimo de Oliveira Cardoso  1 ,  Lucianna Rabelo Pessoa de Siqueira  2 ,  Elany Barbosa da Silva  2 ,  Lívia Bandeira Costa  2 ,  Marcelo Zaldini Hernandes  2 ,  Marcelo Montenegro Rabello  2 ,  Rafaela Salgado Ferreira  3 ,  Luana Faria da Cruz  3 ,  Diogo Rodrigo Magalhães Moreira  4 ,  Valéria Rêgo Alves Pereira  5 ,  Maria Carolina Accioly Brelaz de Castro  5 ,  Paul V Bernhardt  6 ,  Ana Cristina Lima Leite  2
Affiliations
  • 1. Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil. Electronic address: [email protected].
  • 2. Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil.
  • 3. Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, CEP 31270-901 Belo Horizonte, MG, Brazil.
  • 4. Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, CEP, 40296-750 Salvador, BA, Brazil.
  • 5. Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP, 50670-420 Recife, PE, Brazil.
  • 6. School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane 4072, Australia.
PMID: 25147146 DOI: 10.1016/j.ejmech.2014.08.012
Abstract

The present work reports on the synthesis, anti-Trypanosoma cruzi activities and docking studies of a novel series of 2-(pyridin-2-yl)-1,3-thiazoles derived from 2-pyridine thiosemicarbazone. The majority of these compounds are potent cruzain inhibitors and showed excellent inhibition on the trypomastigote form of the Parasite, and the resulting structure-activity relationships are discussed. Together, these data present a novel series of thiazolyl hydrazones with potential effects against Chagas disease and they could be important leads in continuing development against Chagas disease.

Keywords
2-Pyridine thiosemicarbazone; Chagas disease; Hydrazones; Thiazoles; Trypanosoma cruzi.