title: Phthalimido-thiazoles as building blocks and their effects on the growth and morphology of Trypanosoma cruzi.
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.
authors: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil.
authors: Paulo André Teixeira de Moraes
authors: PA
authors: Gomes
authors: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil.
authors: Arsênio Rodrigues
authors: AR
authors: Oliveira
authors: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil.
authors: Marcos Veríssimo de Oliveira
authors: MV
authors: Cardoso
authors: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil.
authors: Edna de Farias
authors: Ede F
authors: Santiago
authors: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil.
authors: Miria de Oliveira
authors: Mde O
authors: Barbosa
authors: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil.
authors: Lucianna Rabelo Pessoa
authors: LR
authors: de Siqueira
authors: Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, CEP 40296-710 Salvador, BA, Brazil.
authors: Diogo Rodrigo Magalhães
authors: DR
authors: Moreira
authors: Fundação Oswaldo Cruz, Centro de Pesquisas Gonçalo Moniz, CEP 40296-710 Salvador, BA, Brazil.
authors: Tanira Matutino
authors: TM
authors: Bastos
authors: Laboratório de Imunologia Keizo Asami-LIKA/UFPE, CEP, 50670-901 Recife, PE, Brazil.
authors: Fábio André
authors: FA
authors: Brayner
authors: 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.
authors: Milena Botelho Pereira
authors: MB
authors: Soares
authors: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP, 50670-420 Recife, PE, Brazil.
authors: Andresa Pereira de Oliveira
authors: AP
authors: Mendes
authors: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP, 50670-420 Recife, PE, Brazil.
authors: Maria Carolina Accioly Brelaz
authors: MC
authors: de Castro
authors: Centro de Pesquisas Aggeu Magalhães, Fundação Oswaldo Cruz, CEP, 50670-420 Recife, PE, Brazil.
authors: Valéria Rego Alves
authors: VR
authors: Pereira
authors: Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, 50740-520 Recife, PE, Brazil. Electronic address: acllb2003@yahoo.com.br.
authors: Ana Cristina Lima
authors: AC
authors: Leite
mesh_terms: D000818:Animals; D049109:Cell Proliferation / Q000187:drug effects; D002522:Chlorocebus aethiops; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests; D010797:Phthalimides / Q000737:chemistry / Q000494:pharmacology*; D013154:Spleen / Q000166:cytology / Q000187:drug effects; D013844:Thiazoles / Q000737:chemistry / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development*; D014709:Vero Cells
chemical_list: D010797:Phthalimides; D013844:Thiazoles; D014344:Trypanocidal Agents
keywords: Chagas disease; Hydrazone; Phthalimide; Thiazole; Trypanosoma cruzi