Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2016 |
| 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/18097 |
Resumo: | Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brazil (CNPq), Coordernação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de Alagoas (FAPEAL |
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Silva Júnior, E. F.Silva, E. P. S.França, P. H. B.Silva, J. P. N.Barreto, E. O.Silva, E. B.Ferreira, R. S.Gatto, C. C.Moreira, Diogo Rodrigo MagalhãesSiqueira Neto, J. L.Mendonça Júnior, F. J. B.Lima, M. C. A.Bortoluzzi, J. H.Scotti, M. T.Scotti, L.Meneghetti, M. R.Aquino, T. M.Araújo Júnior, João Xavier de2017-03-21T14:15:55Z2017-03-21T14:15:55Z2016SILVA JUNIOR, E. F. et al. Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi. Bioorganic & Medicinal Chemistry, v. 24, p. 4228-4240, 2016.0968-0896https://www.arca.fiocruz.br/handle/icict/1809710.1016/j.bmc.2016.07.013Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brazil (CNPq), Coordernação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de Alagoas (FAPEALFederal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil.Federal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil.Federal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil.Federal University of Alagoas. Cell Biology Laboratory. Maceio, AL, Brazil.Federal University of Alagoas. Cell Biology Laboratory. Maceio, AL, Brazil.Federal University of Minas Gerais. Biological Sciences Institute. Biochemistry and Immunology Department. Minas Gerais, BH, Brazil.Federal University of Minas Gerais. Biological Sciences Institute. Biochemistry and Immunology Department. Minas Gerais, BH, Brazil.University of Brasilia. Institute of Chemistry. Inorganic Synthesis and Crystallography Laboratory. Brasília, DF, Brazil.Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Engenharia Tecidual e Imunofarmacologia. Salvador, BA, Brasil.Skaggs School of Pharmacy and Pharmaceutical Sciences. California, San Diego La Jolla, USA.Laboratory of State University of Paraiba. Drug Synthesis and Delivery. Biological Sciences Department. João Pessoa, PB, Brazil.Federal University of Pernambuco. National Science and Technology Institute for Pharmaceutical Innovation. Drug Design and Synthesis Laboratory. Recife, PE, Brazil.Federal University of Alagoas. Institute of Chemistry and Biotechnology. Catalysis and Chemical Reactivity Group. Maceio, AL, Brazil.Laboratory of State University of Paraiba. Drug Synthesis and Delivery. Biological Sciences Department. João Pessoa, PB, Brazil.Laboratory of State University of Paraiba. Drug Synthesis and Delivery. Biological Sciences Department. João Pessoa, PB, Brazil.Federal University of Alagoas. Institute of Chemistry and Biotechnology. Catalysis and Chemical Reactivity Group. Maceio, AL, Brazil.Federal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil.Federal University of Alagoas. Pharmacy and Nursing School. Medicinal Chemistry Laboratory. Maceio, AL, Brazil.In this study, we designed and synthesized a series of thiophen-2-iminothiazolidine derivatives from thiophen-2-thioureic with good anti-Trypanosoma cruzi activity. Several of the final compounds displayed remarkable trypanocidal activity. The ability of the new compounds to inhibit the activity of the enzyme cruzain, the major cysteine protease of T. cruzi, was also explored. The compounds 3b, 4b, 8b and 8c were the most active derivatives against amastigote form, with significant IC50 values between 9.7 and 6.03μM. The 8c derivative showed the highest potency against cruzain (IC50=2.4μM). Molecular docking study showed that this compound can interact with subsites S1 and S2 simultaneously, and the negative values for the theoretical energy binding (Eb=-7.39kcal·mol(-1)) indicates interaction (via dipole-dipole) between the hybridized sulfur sp(3) atom at the thiazolidine ring and Gly66. Finally, the results suggest that the thiophen-2-iminothiazolidines synthesized are important lead compounds for the continuing battle against Chagas disease.engElsevierTiofenoTiazolidinaT. cruziDoença de ChagasThiopheneThiazolidineDockingT. cruziChagas diseaseDesign, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruziinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo: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/18097/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALSilva Junior EF Design, synthesis....pdfSilva Junior EF Design, 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| dc.title.pt_BR.fl_str_mv |
Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi |
| title |
Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi |
| spellingShingle |
Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi Silva Júnior, E. F. Tiofeno Tiazolidina T. cruzi Doença de Chagas Thiophene Thiazolidine Docking T. cruzi Chagas disease |
| title_short |
Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi |
| title_full |
Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi |
| title_fullStr |
Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi |
| title_full_unstemmed |
Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi |
| title_sort |
Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi |
| author |
Silva Júnior, E. F. |
| author_facet |
Silva Júnior, E. F. Silva, E. P. S. França, P. H. B. Silva, J. P. N. Barreto, E. O. Silva, E. B. Ferreira, R. S. Gatto, C. C. Moreira, Diogo Rodrigo Magalhães Siqueira Neto, J. L. Mendonça Júnior, F. J. B. Lima, M. C. A. Bortoluzzi, J. H. Scotti, M. T. Scotti, L. Meneghetti, M. R. Aquino, T. M. Araújo Júnior, João Xavier de |
| author_role |
author |
| author2 |
Silva, E. P. S. França, P. H. B. Silva, J. P. N. Barreto, E. O. Silva, E. B. Ferreira, R. S. Gatto, C. C. Moreira, Diogo Rodrigo Magalhães Siqueira Neto, J. L. Mendonça Júnior, F. J. B. Lima, M. C. A. Bortoluzzi, J. H. Scotti, M. T. Scotti, L. Meneghetti, M. R. Aquino, T. M. Araújo Júnior, João Xavier de |
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author author author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Silva Júnior, E. F. Silva, E. P. S. França, P. H. B. Silva, J. P. N. Barreto, E. O. Silva, E. B. Ferreira, R. S. Gatto, C. C. Moreira, Diogo Rodrigo Magalhães Siqueira Neto, J. L. Mendonça Júnior, F. J. B. Lima, M. C. A. Bortoluzzi, J. H. Scotti, M. T. Scotti, L. Meneghetti, M. R. Aquino, T. M. Araújo Júnior, João Xavier de |
| dc.subject.other.pt_BR.fl_str_mv |
Tiofeno Tiazolidina T. cruzi Doença de Chagas |
| topic |
Tiofeno Tiazolidina T. cruzi Doença de Chagas Thiophene Thiazolidine Docking T. cruzi Chagas disease |
| dc.subject.en.pt_BR.fl_str_mv |
Thiophene Thiazolidine Docking T. cruzi Chagas disease |
| description |
Conselho Nacional de Desenvolvimento Científico e Tecnológico – Brazil (CNPq), Coordernação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) and Fundação de Amparo à Pesquisa do Estado de Alagoas (FAPEAL |
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2016 |
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2016 |
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2017-03-21T14:15:55Z |
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2017-03-21T14:15:55Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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SILVA JUNIOR, E. F. et al. Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi. Bioorganic & Medicinal Chemistry, v. 24, p. 4228-4240, 2016. |
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https://www.arca.fiocruz.br/handle/icict/18097 |
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0968-0896 |
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10.1016/j.bmc.2016.07.013 |
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SILVA JUNIOR, E. F. et al. Design, synthesis, molecular docking and biological evaluation of thiophen-2-iminothiazolidine derivatives for use against Trypanosoma cruzi. Bioorganic & Medicinal Chemistry, v. 24, p. 4228-4240, 2016. 0968-0896 10.1016/j.bmc.2016.07.013 |
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Elsevier |
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Elsevier |
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