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

Autor:	Gomes PA; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil., Oliveira AR; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil., Cardoso MV; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil., Santiago Ede F; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil., Barbosa Mde O; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil., de Siqueira LR; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil., Moreira DR; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, CEP 40296-710 Salvador, BA, Brazil., Bastos TM; Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, CEP 40296-710 Salvador, BA, Brazil., Brayner FA; Laboratório de Imunologia Keizo Asami-LIKA/UFPE, CEP, 50670-901 Recife, PE, Brazil., Soares MB; 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., Mendes AP; Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP, 50670-420 Recife, PE, Brazil., de Castro MC; Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP, 50670-420 Recife, PE, Brazil., Pereira VR; Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP, 50670-420 Recife, PE, Brazil., Leite AC; Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil. Electronic address: acllb2003@yahoo.com.br.
Jazyk:	angličtina
Zdroj:	European journal of medicinal chemistry [Eur J Med Chem] 2016 Mar 23; Vol. 111, pp. 46-57. Date of Electronic Publication: 2016 Jan 11.
DOI:	10.1016/j.ejmech.2016.01.010
Abstrakt:	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. (Copyright © 2016 Elsevier Masson SAS. All rights reserved.)
Databáze:	MEDLINE
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