New 1,3-thiazole derivatives and their biological and ultrastructural effects on Trypanosoma cruzi.
In previous studies, the compound 3-(bromopropiophenone) thiosemicarbazone was described as a potent anti-Trypanosoma cruzi and cruzain inhibitor. In view to optimize this activity, 1,3-thiazole core was used as building-block strategy to access new lead generation of anti T. cruzi agents. In this way a series of thiazole derivatives were synthesized and most of these derivatives exhibited antiparasitic activity similar to benznidazole (Bzd). Among them, compounds (1c) and (1g) presented better selective index (SI) than Bzd. In addition, compounds showed inhibitory activity against the cruzain protease. As observed by electron microscopy, compound (1c) treatment caused irreversible and specific morphological changes on ultrastructure organization of T. cruzi, demonstrating that this class of compounds is killing parasites.
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil.
Paulo André Teixeira
PAT
de Moraes Gomes
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil.
Miria
M
de Oliveira Barbosa
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil.
Edna
E
Farias Santiago
Universidade de Pernambuco, 56328-903, Petrolina, PE, Brazil.
Marcos Veríssimo
MV
de Oliveira Cardoso
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil.
Natáli Tereza
NT
Capistrano Costa
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil.
Marcelo Zaldini
MZ
Hernandes
Centro de Pesquisas Gonçalo Moniz, Fundação Oswaldo Cruz, CEP 40296-750, Salvador, BA, Brazil.
Diogo Rodrigo Magalhães
DRM
Moreira
Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP 50670-420, Recife, PE, Brazil.
Aline Caroline
AC
da Silva
Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP 50670-420, Recife, PE, Brazil.
Thiago André Ramos
TAR
Dos Santos
Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP 50670-420, Recife, PE, Brazil.
Valéria Rêgo Alves
VRA
Pereira
Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP 50670-420, Recife, PE, Brazil.
Fábio André
FA
Brayner Dos Santosd
CAPES Foundation, Ministry of Education of Brazil, Brasília, DF, Brazil; Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil.
Glaécia Aparecida
GA
do Nascimento Pereira
Departamento de Bioquímica e Imunologia, Universidade Federal de Minas Gerais, CEP 31270-901, Belo Horizonte, MG, Brazil.
Rafaela Salgado
RS
Ferreira
Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520, Recife, PE, Brazil. Electronic address: acllb2003@yahoo.com.br.
Ana Cristina Lima
ACL
Leite
D000818:Animals; D002522:Chlorocebus aethiops; D003546:Cysteine Endopeptidases / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D051379:Mice; D062105:Molecular Docking Simulation; D011487:Protein Conformation; D015800:Protozoan Proteins / Q000737:chemistry / Q000378:metabolism; D013844:Thiazoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure*; D014709:Vero Cells
D015800:Protozoan Proteins; D013844:Thiazoles; D014344:Trypanocidal Agents; D003546:Cysteine Endopeptidases; C074032:cruzain, Trypanosoma cruzi
Antiprotozoal agents; Chagas disease; Cruzain; Electron microscopy; Hydrazones; Thiazole