Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2015 |
| Outros Autores: | , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/13781 |
Resumo: | Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil. |
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Oliveira Filho, Gevanio Bezerra deCardoso, Marcos Veríssimo de OliveiraEspíndola, José Wanderlan PontesFerreira, Luiz Felipe Gomes RebelloSimone, Carlos Alberto deFerreira, Rafaela SalgadoCoelho, Pollyanne LacerdaMeira, Cássio SantanaMoreira, Diogo Rodrigo MagalhãesSoares, Milena Botelho PereiraLeite, Ana Cristina Lima2016-04-14T17:12:17Z2016-04-14T17:12:17Z2015OLIVEIRA FILHO, G. B. et al. Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi. Bioorganic & Medicinal Chemistry, v. 23, n. 23, p. 7478-7486, 2015.1464-3391https://www.arca.fiocruz.br/handle/icict/1378110.1016/j.bmc.2015.10.048engElsevierStructural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil.Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil.Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil.Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil.Universidade de São Paulo. Instituto de Física. Departamento de Física e Informática. São Carlos, SP, Brasil.Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, Brasil / Hospital São Rafael. Centro de Biotecnologia e Terapia Celular. Salvador, BA, Brasil.Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil.Chagas disease is an infection caused by protozoan Trypanosoma cruzi, which affects approximately 8-10million people worldwide. Benznidazole is the only drug approved for treatment during the acute and asymptomatic chronic phases of Chagas disease; however, it has poor efficacy during the symptomatic chronic phase. Therefore, the development of new pharmaceuticals is needed. Here, we employed the bioisosterism to modify a potent antiparasitic and cruzain-inhibitor aryl thiosemicarbazone (4) into 4-thiazolidinones (7-21). Compounds (7-21) were prepared by using a straightforward synthesis and enabled good to excellent yields. As a chemical elucidation tool, X-ray diffraction of compound (10) revealed the geometry and conformation of this class compounds. The screening against cruzain showed that 4-thiazolidinones were less active than thiosemicarbazone (4). However, the antiparasitic activity in Y strain trypomastigotes and host cell cytotoxicity in J774 macrophages revealed that compounds (10 and 18-21) are stronger and more selective antiparasitic agents than thiosemicarbazone (4). Specifically, compounds (18-20), which carry a phenyl at position N3 of heterocyclic ring, were the most active ones, suggesting that this is a structural determinant for activity. In infected macrophages, compounds (18-20) reduced intracellular amastigotes, whereas Benznidazole did not. In T. cruzi-infected mice treated orally with 100mg/kg of compound (20), a decreased of parasitemia was observed. In conclusion, we demonstrated that the conversation of thiosemicarbazones into 4-thiazolidinones retains pharmacological property while enhances selectivity.Chagas diseaseTrypanosoma cruziThiosemicarbazonesThiazolidinonesBioisosterisminfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZORIGINALOliveira Filho GB Structural ....pdfOliveira Filho GB Structural ....pdfapplication/pdf933867https://www.arca.fiocruz.br/bitstream/icict/13781/2/Oliveira%20Filho%20GB%20Structural%20....pdf5fa9deec2f28426fcb9014c1143f9035MD52LICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/13781/3/license.txt5a560609d32a3863062d77ff32785d58MD53TEXTOliveira Filho GB Structural ....pdf.txtOliveira Filho GB Structural ....pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi |
| title |
Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi |
| spellingShingle |
Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi Oliveira Filho, Gevanio Bezerra de Chagas disease Trypanosoma cruzi Thiosemicarbazones Thiazolidinones Bioisosterism |
| title_short |
Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi |
| title_full |
Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi |
| title_fullStr |
Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi |
| title_full_unstemmed |
Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi |
| title_sort |
Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi |
| author |
Oliveira Filho, Gevanio Bezerra de |
| author_facet |
Oliveira Filho, Gevanio Bezerra de Cardoso, Marcos Veríssimo de Oliveira Espíndola, José Wanderlan Pontes Ferreira, Luiz Felipe Gomes Rebello Simone, Carlos Alberto de Ferreira, Rafaela Salgado Coelho, Pollyanne Lacerda Meira, Cássio Santana Moreira, Diogo Rodrigo Magalhães Soares, Milena Botelho Pereira Leite, Ana Cristina Lima |
| author_role |
author |
| author2 |
Cardoso, Marcos Veríssimo de Oliveira Espíndola, José Wanderlan Pontes Ferreira, Luiz Felipe Gomes Rebello Simone, Carlos Alberto de Ferreira, Rafaela Salgado Coelho, Pollyanne Lacerda Meira, Cássio Santana Moreira, Diogo Rodrigo Magalhães Soares, Milena Botelho Pereira Leite, Ana Cristina Lima |
| author2_role |
author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Oliveira Filho, Gevanio Bezerra de Cardoso, Marcos Veríssimo de Oliveira Espíndola, José Wanderlan Pontes Ferreira, Luiz Felipe Gomes Rebello Simone, Carlos Alberto de Ferreira, Rafaela Salgado Coelho, Pollyanne Lacerda Meira, Cássio Santana Moreira, Diogo Rodrigo Magalhães Soares, Milena Botelho Pereira Leite, Ana Cristina Lima |
| dc.subject.en.pt_BR.fl_str_mv |
Chagas disease Trypanosoma cruzi Thiosemicarbazones Thiazolidinones Bioisosterism |
| topic |
Chagas disease Trypanosoma cruzi Thiosemicarbazones Thiazolidinones Bioisosterism |
| description |
Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil. |
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2015 |
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2015 |
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2016-04-14T17:12:17Z |
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2016-04-14T17:12:17Z |
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OLIVEIRA FILHO, G. B. et al. Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi. Bioorganic & Medicinal Chemistry, v. 23, n. 23, p. 7478-7486, 2015. |
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https://www.arca.fiocruz.br/handle/icict/13781 |
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1464-3391 |
| dc.identifier.doi.none.fl_str_mv |
10.1016/j.bmc.2015.10.048 |
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OLIVEIRA FILHO, G. B. et al. Structural design, synthesis and pharmacological evaluation of 4-thiazolidinones against Trypanosoma cruzi. Bioorganic & Medicinal Chemistry, v. 23, n. 23, p. 7478-7486, 2015. 1464-3391 10.1016/j.bmc.2015.10.048 |
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