Phthalimido-thiazoles as building blocks and their effects on the growth and morphology of Trypanosoma cruzi

  • Eur J Med Chem. 2016 Mar 23:111:46-57. doi: 10.1016/j.ejmech.2016.01.010.
Paulo André Teixeira de Moraes Gomes  1 ,  Arsênio Rodrigues Oliveira  1 ,  Marcos Veríssimo de Oliveira Cardoso  1 ,  Edna de Farias Santiago  1 ,  Miria de Oliveira Barbosa  1 ,  Lucianna Rabelo Pessoa de Siqueira  1 ,  Diogo Rodrigo Magalhães Moreira  2 ,  Tanira Matutino Bastos  2 ,  Fábio André Brayner  3 ,  Milena Botelho Pereira Soares  4 ,  Andresa Pereira de Oliveira Mendes  5 ,  Maria Carolina Accioly Brelaz de Castro  5 ,  Valéria Rego Alves Pereira  5 ,  Ana Cristina Lima Leite  6
Affiliations
  • 1. Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil.
  • 2. Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, CEP 40296-710 Salvador, BA, Brazil.
  • 3. Laboratório de Imunologia Keizo Asami-LIKA/UFPE, CEP, 50670-901 Recife, PE, Brazil.
  • 4. Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, CEP 40296-710 Salvador, BA, Brazil; Centro de Biotecnologia e Terapia Celular, Hospital São Rafael, Avenida São Rafael, 2152, São Marcos, CEP 41253-190, Salvador BA, Brazil.
  • 5. Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP, 50670-420 Recife, PE, Brazil.
  • 6. Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil. Electronic address: [email protected].
PMID: 26854377 DOI: 10.1016/j.ejmech.2016.01.010
Abstract

Chagas disease is a parasitic Infection caused by protozoan Trypanosoma cruzi that affects approximately 6-7 million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases; however, its efficacy during the symptomatic chronic phase is controversial. The present work reports the synthesis and anti-T. cruzi activities of a novel series of phthalimido-thiazoles. Some of these compounds showed potent inhibition of the trypomastigote form of the Parasite at low cytotoxicity concentrations in spleen cells, and the resulting structure-activity relationships are discussed. We also showed that phthalimido-thiazoles induced ultrastructural alterations on morphology, flagellum shortening, chromatin condensation, mitochondria swelling, reservosomes alterations and endoplasmic reticulum dilation. Together, these data revealed, for the first time, a novel series of phthalimido-thiazoles-structure-based compounds with potential effects against T. cruzi and lead-like characteristics against Chagas disease.

Keywords
Chagas disease; Hydrazone; Phthalimide; Thiazole; Trypanosoma cruzi.