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Structural design, synthesis and anti-Trypanosoma cruzi profile of the second generation of 4-thiazolidinones chlorine derivatives.
Bezerra de Oliveira Filho, Gevanio; Veríssimo de Oliveira Cardoso, Marcos; Caroline da Silva Santos, Aline; Ramos Dos Santos, Thiago André; Cristovão-Silva, Ana Catarina; Rubio, Laura González; da Silva Maia Neto, Luiz; Leite, Paulo Gaio; Machado, Fabiana Simão; Alves, Luiz Carlos; Brayner, Fabio André; Alves Pereira, Valéria Rêgo; Lima Leite, Ana Cristina.
Afiliação
  • Bezerra de Oliveira Filho G; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, 50740-520, Recife, PE, Brazil.
  • Veríssimo de Oliveira Cardoso M; Laboratory of Prospecting Bioactive Molecules, University of Pernambuco, 56328-903, Petrolina, PE, Brazil.
  • Caroline da Silva Santos A; Department of Immunology, Laboratory of Immunopathology and Molecular Biology, IAM / FIOCRUZ, 50740-465, Recife, PE, Brazil.
  • Ramos Dos Santos TA; Department of Immunology, Laboratory of Immunopathology and Molecular Biology, IAM / FIOCRUZ, 50740-465, Recife, PE, Brazil.
  • Cristovão-Silva AC; Department of Immunology, Laboratory of Immunopathology and Molecular Biology, IAM / FIOCRUZ, 50740-465, Recife, PE, Brazil.
  • Rubio LG; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, 50740-520, Recife, PE, Brazil.
  • da Silva Maia Neto L; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, 50740-520, Recife, PE, Brazil.
  • Leite PG; Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
  • Machado FS; Department of Biochemistry and Immunology, Institute of Biological Sciences, Federal University of Minas Gerais, 31270-901, Belo Horizonte, MG, Brazil.
  • Alves LC; Laboratory of Immunopathology Keizo Asami-LIKA / UFPE, 50670-420, Recife, PE, Brazil; Department of Parasitology, Cellular and Molecular Biology Laboratories, Leishmaniasis, and Mutagenesis, IAM / FIOCRUZ, 50740-465, Recife, PE, Brazil.
  • Brayner FA; Laboratory of Immunopathology Keizo Asami-LIKA / UFPE, 50670-420, Recife, PE, Brazil; Department of Parasitology, Cellular and Molecular Biology Laboratories, Leishmaniasis, and Mutagenesis, IAM / FIOCRUZ, 50740-465, Recife, PE, Brazil.
  • Alves Pereira VR; Department of Immunology, Laboratory of Immunopathology and Molecular Biology, IAM / FIOCRUZ, 50740-465, Recife, PE, Brazil.
  • Lima Leite AC; Department of Pharmaceutical Sciences, Health Sciences Center, Federal University of Pernambuco, 50740-520, Recife, PE, Brazil. Electronic address: ana.lleite@ufpe.br.
Chem Biol Interact ; 345: 109514, 2021 Aug 25.
Article em En | MEDLINE | ID: mdl-34023282
Chagas disease causes more deaths in the Americas than any other parasitic disease. Initially confined to the American continent, it is increasingly becoming a global health problem. In fact, it is considered to be an "exotic" disease in Europe, being virtually undiagnosed. Benznidazole, the only drug approved for treatment, effectively treats acute-stage Chagas disease, but its effectiveness for treating indeterminate and chronic stages remains uncertain. Previously, our research group demonstrated that 4-thiazolidinones presented anti-T. cruzi activity including in the in vivo assays in mice, making this fragment appealing for drug development. The present work reports the synthesis and anti-T. cruzi activities of a novel series of 4-thiazolidinones derivatives that resulted in an increased anti-T. cruzi activity in comparison to thiosemicarbazones intermediates. Compounds 2c, 2e, and 3a showed potent inhibition of the trypomastigote form of the parasite at low cytotoxicity concentrations in mouse splenocytes. Besides, all the 2c, 2e, and 3a tested concentrations showed no cytotoxic activity on macrophages cell viability. When macrophages were submitted to T. cruzi infection and treated with 2c and 3a, compounds reduced the release of trypomastigote forms. Results also showed that the increased trypanocidal activity induced by 2c and 3a is independent of nitric oxide release. Flow cytometry assay showed that compound 2e was able to induce necrosis and apoptosis in trypomastigotes. Parasites treated with the compounds 2e, 3a, and 3c presented flagellum shortening, retraction and curvature of the parasite body, and extravasation of the internal content. Together, these data revealed a novel series of 4-thiazolidinones fragment-based compounds with potential effects against T. cruzi and lead-like characteristics.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tripanossomicidas / Trypanosoma cruzi / Desenho de Fármacos / Cloro / Tiazolidinas Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Chem Biol Interact Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Irlanda
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Tripanossomicidas / Trypanosoma cruzi / Desenho de Fármacos / Cloro / Tiazolidinas Tipo de estudo: Prognostic_studies Limite: Animals Idioma: En Revista: Chem Biol Interact Ano de publicação: 2021 Tipo de documento: Article País de afiliação: Brasil País de publicação: Irlanda