Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| Outros Autores: | , , , , , , , , |
| Tipo de documento: | Artigo de conferência |
| Idioma: | eng |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/18001 |
Resumo: | FACEPE, CAPES, CNPq. |
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Barbosa, Miria de OliveiraOliveira Filho, Gevanio Bezerra deSiqueira, Lucianna Râbelo Pessôa deOliveira, Arsênio RodriguesMiranda Filho, Carlos André LaranjeiraOliveira, Ulisses José Félix Tenório deMoreira, Diogo Rodrigo MagalhãesMeira, Cássio SantanaSoares, Milena Botelho PereiraLeite, Ana Cristina Lima2017-03-09T18:47:28Z2017-03-09T18:47:28Z2016BARBOSA, M. O. et al. Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles. In: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 52., Alagoas, 2016. Anais eletrônicos... Alagoas: Sociedade Brasileira de Medicina Tropical, 2016. p. 10586.https://www.arca.fiocruz.br/handle/icict/18001FACEPE, CAPES, CNPq.UFPE. Laboratório de Planejamento em Química Medicinal – LpQM. Recife, PE, BrasilUFPE. Laboratório de Planejamento em Química Medicinal – LpQM. Recife, PE, BrasilUFPE. Laboratório de Planejamento em Química Medicinal – LpQM. Recife, PE, BrasilUFPE. Laboratório de Planejamento em Química Medicinal – LpQM. Recife, PE, BrasilUFPE. Laboratório de Planejamento em Química Medicinal – LpQM. Recife, PE, BrasilUFPE. Laboratório de Planejamento em Química Medicinal – LpQM. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, BrasilUFPE. Laboratório de Planejamento em Química Medicinal – LpQM. Recife, PE, BrasilChagas disease is a parasitic infection caused by protozoan T. cruzi, which affects around 7 million people worldwide. Benznidazole (BZD) is the sole drug approved for treatment during the acute and asymptomatic chronic phases, however it has not efficacy during the chronic phase. Therefore, the development of new medicines is needed. To identify new trypanocidal compounds, we performed a structural planning and synthesis of new aryl-1,3-thiazoles (LpQM-7-28). Aryl-4-thiazoles were designed with the aim to identify less cytotoxic and more potent trypanocidal agents than the thiosemicarbazones (Int1-3). We also looked for understand most the structure-anti-T. cruzi activity relationships for this class of thiazoles, thus several substituents were attached to the N3 and C4 position of the heterocyclic ring. The trypanocidal activity was determined for Y strain trypomastigotes and the toxicity was measured for J774 macrophages. After the screening for compounds, it was possible to identify the compounds (LpQM-12, 15, 16, 21, 23 and LpQM-26) as trypanocidal agents equipotent to BZD but with the advantage of these displayed low toxicity for macrophages. These compounds have as common structural feature a 4-metoxi-phenyl, or 4-methyl-pheny, or phenyl or pyridyl group attached at C4, suggesting theses groups are important for warrant anti-T. cruzi activity. The inserting alkyl substituents at the 5-position of the heterocycle increased pharmacological activity, and should be explored by our research group. Five of most active compounds for tripomastigote form (LpQM-7, 9, 12, 16 and LpQM-23) present more of 70% of inhibitory activity of cruzain, suggesting a possible mechanism of action these compounds. Overall, we have shown here that thiazoles are endowed with trypanocidal activity greater than thiosemicarbazones (Int1-3), besides of being more selective in regard to toxicity in macrophages, therefore suggesting these thiazoles are potential anti-T. cruzi drug prototypes.engSociedade Brasileira de Medicina TropicalDoença de ChagasTrypanosoma cruzi1,3-thiazolesChagas diseaseTrypanosoma cruzi1,3-thiazolesStructural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazolesinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/conferenceObject2016-08-21MaceióCongresso da Sociedade Brasileira de Medicina Tropicalbiennialinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/18001/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALBarbosa MO 10586-Structural-planning-synthesis-and-evaluation-of-properties-trypanocidal-aryl-13-thiazoles.pdfBarbosa MO 10586-Structural-planning-synthesis-and-evaluation-of-properties-trypanocidal-aryl-13-thiazoles.pdfapplication/pdf101049https://www.arca.fiocruz.br/bitstream/icict/18001/2/Barbosa%20MO%2010586-Structural-planning-synthesis-and-evaluation-of-properties-trypanocidal-aryl-13-thiazoles.pdf856a8138891dbcdce59b2038f6c550b4MD52TEXTBarbosa MO 10586-Structural-planning-synthesis-and-evaluation-of-properties-trypanocidal-aryl-13-thiazoles.pdf.txtBarbosa MO 10586-Structural-planning-synthesis-and-evaluation-of-properties-trypanocidal-aryl-13-thiazoles.pdf.txtExtracted texttext/plain2756https://www.arca.fiocruz.br/bitstream/icict/18001/3/Barbosa%20MO%2010586-Structural-planning-synthesis-and-evaluation-of-properties-trypanocidal-aryl-13-thiazoles.pdf.txt92413a5c9840ce88b7496733393b1312MD53icict/180012018-08-15 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| dc.title.pt_BR.fl_str_mv |
Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles |
| title |
Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles |
| spellingShingle |
Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles Barbosa, Miria de Oliveira Doença de Chagas Trypanosoma cruzi 1,3-thiazoles Chagas disease Trypanosoma cruzi 1,3-thiazoles |
| title_short |
Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles |
| title_full |
Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles |
| title_fullStr |
Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles |
| title_full_unstemmed |
Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles |
| title_sort |
Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles |
| author |
Barbosa, Miria de Oliveira |
| author_facet |
Barbosa, Miria de Oliveira Oliveira Filho, Gevanio Bezerra de Siqueira, Lucianna Râbelo Pessôa de Oliveira, Arsênio Rodrigues Miranda Filho, Carlos André Laranjeira Oliveira, Ulisses José Félix Tenório de Moreira, Diogo Rodrigo Magalhães Meira, Cássio Santana Soares, Milena Botelho Pereira Leite, Ana Cristina Lima |
| author_role |
author |
| author2 |
Oliveira Filho, Gevanio Bezerra de Siqueira, Lucianna Râbelo Pessôa de Oliveira, Arsênio Rodrigues Miranda Filho, Carlos André Laranjeira Oliveira, Ulisses José Félix Tenório de Moreira, Diogo Rodrigo Magalhães Meira, Cássio Santana Soares, Milena Botelho Pereira Leite, Ana Cristina Lima |
| author2_role |
author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Barbosa, Miria de Oliveira Oliveira Filho, Gevanio Bezerra de Siqueira, Lucianna Râbelo Pessôa de Oliveira, Arsênio Rodrigues Miranda Filho, Carlos André Laranjeira Oliveira, Ulisses José Félix Tenório de Moreira, Diogo Rodrigo Magalhães Meira, Cássio Santana Soares, Milena Botelho Pereira Leite, Ana Cristina Lima |
| dc.subject.other.pt_BR.fl_str_mv |
Doença de Chagas Trypanosoma cruzi 1,3-thiazoles |
| topic |
Doença de Chagas Trypanosoma cruzi 1,3-thiazoles Chagas disease Trypanosoma cruzi 1,3-thiazoles |
| dc.subject.en.pt_BR.fl_str_mv |
Chagas disease Trypanosoma cruzi 1,3-thiazoles |
| description |
FACEPE, CAPES, CNPq. |
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2016 |
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2016 |
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2017-03-09T18:47:28Z |
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2017-03-09T18:47:28Z |
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BARBOSA, M. O. et al. Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles. In: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 52., Alagoas, 2016. Anais eletrônicos... Alagoas: Sociedade Brasileira de Medicina Tropical, 2016. p. 10586. |
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https://www.arca.fiocruz.br/handle/icict/18001 |
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BARBOSA, M. O. et al. Structural planning, synthesis and evaluation of properties trypanocidal aryl-1,3-thiazoles. In: CONGRESSO DA SOCIEDADE BRASILEIRA DE MEDICINA TROPICAL, 52., Alagoas, 2016. Anais eletrônicos... Alagoas: Sociedade Brasileira de Medicina Tropical, 2016. p. 10586. |
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Sociedade Brasileira de Medicina Tropical |
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Sociedade Brasileira de Medicina Tropical |
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