In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2023 |
| Outros Autores: | , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/58450 https://doi.org/10.1038/s41598-023-34124-9 |
Resumo: | Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Londrina, PR, Brasil. |
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Schirmann, Jéseka G.Bortoleti, Bruna T. S.Gonçalves, Manoela D.Tomiotto‑Pellissier, FernandaCamargo, Priscila G.Miranda‑Sapla, Milena M.Lima, Camilo H. S.Bispo, Marcelle L. F.Costa, Idessania N.Conchon‑Costa, IvetePavanelli, Wander R.Dekker, Robert F. H.Barbosa‑Dekker, Aneli M.2023-05-16T19:47:39Z2023-05-16T19:47:39Z2023SCHIRMANN, Jéseka G. et al. In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphenyl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential. Scientific Reports, v. 17, p. 1-11, 2023.2045-2322https://www.arca.fiocruz.br/handle/icict/58450https://doi.org/10.1038/s41598-023-34124-9porNature ResearchIn‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potentialinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Londrina, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Programa de Pós-Graduação em Biociências e Biotecnologia. Curitiba, PR, Brasil. / Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Londrina, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Programa de Pós-Graduação em Biociências e Biotecnologia. Curitiba, PR, Brasil. / Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Londrina, PR, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Londrina, PR, Brasil.Universidade Tecnológica Federal do Paraná. Programa de Pós-Graduação em Engenharia Ambiental. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Londrina, PR, Brasil.Available treatments for leishmaniasis have been widely used since the 1940s but come at a high cost, variable efcacy, high toxicity, and adverse side effects. 3,3′,5,5′-Tetramethoxy-biphenyl4,4′-diol (TMBP) was synthesized through laccase-catalysis of 2,6-dimethoxyphenol and displayed antioxidant and anticancer activity, and is considered a potential drug candidate. Thus, this study aimed to evaluate the anti-leishmanial efect of TMBP against promastigote and amastigote forms of Leishmania (L.) amazonensis and investigated the mechanisms involved in parasite death. TMBP treatment inhibited the proliferation (IC50 0.62–0.86 µM) and induced the death of promastigote forms by generating reactive oxygen species and mitochondrial dysfunction. In intracellular amastigotes, TMBP reduced the percentage of infected macrophages, being 62.7 times more selective to the parasite (CC50 53.93 µM). TMBP did not hemolyze sheep erythrocytes; indicative of low cytotoxicity. Additionally, molecular docking analysis on two enzyme targets of L. amazonensis: trypanothione reductase (TR) and leishmanolysin (Gp63), suggested that the hydroxyl group could be a pharmacophoric group due to its binding afnity by hydrogen bonds with residues at the active site of both enzymes. TMBP was more selective to the Gp63 target than TR. This is the frst report that TMBP is a promising compound to act as an anti-leishmanial agent.LeishmaniasisDrug-Related Side Effects and Adverse ReactionsParasitesLeishmaniasisEfectos Colaterales y Reacciones Adversas Relacionados con MedicamentosParásitosEffets secondaires indésirables des médicamentsParasitesLeishmaniaLeishmanioseEfeitos Colaterais e Reações Adversas Relacionados a MedicamentosParasitosinfo: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/58450/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINAL41598_2023_Article_34124OK.pdf41598_2023_Article_34124OK.pdfapplication/pdf1903624https://www.arca.fiocruz.br/bitstream/icict/58450/2/41598_2023_Article_34124OK.pdfc8f2e9be419d34de833e6c5fa8b07cc5MD52icict/584502023-05-16 16:47:42.013oai:www.arca.fiocruz.br:icict/58450Q0VTU8ODTyBOw4NPIEVYQ0xVU0lWQSBERSBESVJFSVRPUyBBVVRPUkFJUwoKQW8gYWNlaXRhciBvcyBURVJNT1MgZSBDT05EScOHw5VFUyBkZXN0YSBDRVNTw4NPLCBvIEFVVE9SIGUvb3UgVElUVUxBUiBkZSBkaXJlaXRvcwphdXRvcmFpcyBzb2JyZSBhIE9CUkEgZGUgcXVlIHRyYXRhIGVzdGUgZG9jdW1lbnRvOgoKKDEpIENFREUgZSBUUkFOU0ZFUkUsIHRvdGFsIGUgZ3JhdHVpdGFtZW50ZSwgw6AgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaLCBlbQpjYXLDoXRlciBwZXJtYW5lbnRlLCBpcnJldm9nw6F2ZWwgZSBOw4NPIEVYQ0xVU0lWTywgdG9kb3Mgb3MgZGlyZWl0b3MgcGF0cmltb25pYWlzIE7Dg08KQ09NRVJDSUFJUyBkZSB1dGlsaXphw6fDo28gZGEgT0JSQSBhcnTDrXN0aWNhIGUvb3UgY2llbnTDrWZpY2EgaW5kaWNhZGEgYWNpbWEsIGluY2x1c2l2ZSBvcyBkaXJlaXRvcwpkZSB2b3ogZSBpbWFnZW0gdmluY3VsYWRvcyDDoCBPQlJBLCBkdXJhbnRlIHRvZG8gbyBwcmF6byBkZSBkdXJhw6fDo28gZG9zIGRpcmVpdG9zIGF1dG9yYWlzLCBlbQpxdWFscXVlciBpZGlvbWEgZSBlbSB0b2RvcyBvcyBwYcOtc2VzOwoKKDIpIEFDRUlUQSBxdWUgYSBjZXNzw6NvIHRvdGFsIG7Do28gZXhjbHVzaXZhLCBwZXJtYW5lbnRlIGUgaXJyZXZvZ8OhdmVsIGRvcyBkaXJlaXRvcyBhdXRvcmFpcwpwYXRyaW1vbmlhaXMgbsOjbyBjb21lcmNpYWlzIGRlIHV0aWxpemHDp8OjbyBkZSBxdWUgdHJhdGEgZXN0ZSBkb2N1bWVudG8gaW5jbHVpLCBleGVtcGxpZmljYXRpdmFtZW50ZSwKb3MgZGlyZWl0b3MgZGUgZGlzcG9uaWJpbGl6YcOnw6NvIGUgY29tdW5pY2HDp8OjbyBww7pibGljYSBkYSBPQlJBLCBlbSBxdWFscXVlciBtZWlvIG91IHZlw61jdWxvLAppbmNsdXNpdmUgZW0gUmVwb3NpdMOzcmlvcyBEaWdpdGFpcywgYmVtIGNvbW8gb3MgZGlyZWl0b3MgZGUgcmVwcm9kdcOnw6NvLCBleGliacOnw6NvLCBleGVjdcOnw6NvLApkZWNsYW1hw6fDo28sIHJlY2l0YcOnw6NvLCBleHBvc2nDp8OjbywgYXJxdWl2YW1lbnRvLCBpbmNsdXPDo28gZW0gYmFuY28gZGUgZGFkb3MsIHByZXNlcnZhw6fDo28sIGRpZnVzw6NvLApkaXN0cmlidWnDp8OjbywgZGl2dWxnYcOnw6NvLCBlbXByw6lzdGltbywgdHJhZHXDp8OjbywgZHVibGFnZW0sIGxlZ2VuZGFnZW0sIGluY2x1c8OjbyBlbSBub3ZhcyBvYnJhcyBvdQpjb2xldMOibmVhcywgcmV1dGlsaXphw6fDo28sIGVkacOnw6NvLCBwcm9kdcOnw6NvIGRlIG1hdGVyaWFsIGRpZMOhdGljbyBlIGN1cnNvcyBvdSBxdWFscXVlciBmb3JtYSBkZQp1dGlsaXphw6fDo28gbsOjbyBjb21lcmNpYWw7CgooMykgUkVDT05IRUNFIHF1ZSBhIGNlc3PDo28gYXF1aSBlc3BlY2lmaWNhZGEgY29uY2VkZSDDoCBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPCkNSVVogbyBkaXJlaXRvIGRlIGF1dG9yaXphciBxdWFscXVlciBwZXNzb2Eg4oCTIGbDrXNpY2Egb3UganVyw61kaWNhLCBww7pibGljYSBvdSBwcml2YWRhLCBuYWNpb25hbCBvdQplc3RyYW5nZWlyYSDigJMgYSBhY2Vzc2FyIGUgdXRpbGl6YXIgYW1wbGFtZW50ZSBhIE9CUkEsIHNlbSBleGNsdXNpdmlkYWRlLCBwYXJhIHF1YWlzcXVlcgpmaW5hbGlkYWRlcyBuw6NvIGNvbWVyY2lhaXM7CgooNCkgREVDTEFSQSBxdWUgYSBvYnJhIMOpIGNyaWHDp8OjbyBvcmlnaW5hbCBlIHF1ZSDDqSBvIHRpdHVsYXIgZG9zIGRpcmVpdG9zIGFxdWkgY2VkaWRvcyBlIGF1dG9yaXphZG9zLApyZXNwb25zYWJpbGl6YW5kby1zZSBpbnRlZ3JhbG1lbnRlIHBlbG8gY29udGXDumRvIGUgb3V0cm9zIGVsZW1lbnRvcyBxdWUgZmF6ZW0gcGFydGUgZGEgT0JSQSwKaW5jbHVzaXZlIG9zIGRpcmVpdG9zIGRlIHZveiBlIGltYWdlbSB2aW5jdWxhZG9zIMOgIE9CUkEsIG9icmlnYW5kby1zZSBhIGluZGVuaXphciB0ZXJjZWlyb3MgcG9yCmRhbm9zLCBiZW0gY29tbyBpbmRlbml6YXIgZSByZXNzYXJjaXIgYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVogZGUKZXZlbnR1YWlzIGRlc3Blc2FzIHF1ZSB2aWVyZW0gYSBzdXBvcnRhciwgZW0gcmF6w6NvIGRlIHF1YWxxdWVyIG9mZW5zYSBhIGRpcmVpdG9zIGF1dG9yYWlzIG91CmRpcmVpdG9zIGRlIHZveiBvdSBpbWFnZW0sIHByaW5jaXBhbG1lbnRlIG5vIHF1ZSBkaXogcmVzcGVpdG8gYSBwbMOhZ2lvIGUgdmlvbGHDp8O1ZXMgZGUgZGlyZWl0b3M7CgooNSkgQUZJUk1BIHF1ZSBjb25oZWNlIGEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTwpPU1dBTERPIENSVVogZSBhcyBkaXJldHJpemVzIHBhcmEgbyBmdW5jaW9uYW1lbnRvIGRvIHJlcG9zaXTDs3JpbyBpbnN0aXR1Y2lvbmFsIEFSQ0EuCgpBIFBvbMOtdGljYSBJbnN0aXR1Y2lvbmFsIGRlIEFjZXNzbyBBYmVydG8gZGEgRklPQ1JVWiAtIEZVTkRBw4fDg08gT1NXQUxETyBDUlVaIHJlc2VydmEKZXhjbHVzaXZhbWVudGUgYW8gQVVUT1Igb3MgZGlyZWl0b3MgbW9yYWlzIGUgb3MgdXNvcyBjb21lcmNpYWlzIHNvYnJlIGFzIG9icmFzIGRlIHN1YSBhdXRvcmlhCmUvb3UgdGl0dWxhcmlkYWRlLCBzZW5kbyBvcyB0ZXJjZWlyb3MgdXN1w6FyaW9zIHJlc3BvbnPDoXZlaXMgcGVsYSBhdHJpYnVpw6fDo28gZGUgYXV0b3JpYSBlIG1hbnV0ZW7Dp8OjbwpkYSBpbnRlZ3JpZGFkZSBkYSBPQlJBIGVtIHF1YWxxdWVyIHV0aWxpemHDp8Ojby4KCkEgUG9sw610aWNhIEluc3RpdHVjaW9uYWwgZGUgQWNlc3NvIEFiZXJ0byBkYSBGSU9DUlVaIC0gRlVOREHDh8ODTyBPU1dBTERPIENSVVoKcmVzcGVpdGEgb3MgY29udHJhdG9zIGUgYWNvcmRvcyBwcmVleGlzdGVudGVzIGRvcyBBdXRvcmVzIGNvbSB0ZXJjZWlyb3MsIGNhYmVuZG8gYW9zIEF1dG9yZXMKaW5mb3JtYXIgw6AgSW5zdGl0dWnDp8OjbyBhcyBjb25kacOnw7VlcyBlIG91dHJhcyByZXN0cmnDp8O1ZXMgaW1wb3N0YXMgcG9yIGVzdGVzIGluc3RydW1lbnRvcy4KRepositório 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| dc.title.en_US.fl_str_mv |
In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential |
| title |
In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential |
| spellingShingle |
In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential Schirmann, Jéseka G. Leishmaniasis Drug-Related Side Effects and Adverse Reactions Parasites Leishmaniasis Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos Parásitos Effets secondaires indésirables des médicaments Parasites Leishmania Leishmaniose Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos Parasitos |
| title_short |
In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential |
| title_full |
In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential |
| title_fullStr |
In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential |
| title_full_unstemmed |
In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential |
| title_sort |
In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphen yl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential |
| author |
Schirmann, Jéseka G. |
| author_facet |
Schirmann, Jéseka G. Bortoleti, Bruna T. S. Gonçalves, Manoela D. Tomiotto‑Pellissier, Fernanda Camargo, Priscila G. Miranda‑Sapla, Milena M. Lima, Camilo H. S. Bispo, Marcelle L. F. Costa, Idessania N. Conchon‑Costa, Ivete Pavanelli, Wander R. Dekker, Robert F. H. Barbosa‑Dekker, Aneli M. |
| author_role |
author |
| author2 |
Bortoleti, Bruna T. S. Gonçalves, Manoela D. Tomiotto‑Pellissier, Fernanda Camargo, Priscila G. Miranda‑Sapla, Milena M. Lima, Camilo H. S. Bispo, Marcelle L. F. Costa, Idessania N. Conchon‑Costa, Ivete Pavanelli, Wander R. Dekker, Robert F. H. Barbosa‑Dekker, Aneli M. |
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author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Schirmann, Jéseka G. Bortoleti, Bruna T. S. Gonçalves, Manoela D. Tomiotto‑Pellissier, Fernanda Camargo, Priscila G. Miranda‑Sapla, Milena M. Lima, Camilo H. S. Bispo, Marcelle L. F. Costa, Idessania N. Conchon‑Costa, Ivete Pavanelli, Wander R. Dekker, Robert F. H. Barbosa‑Dekker, Aneli M. |
| dc.subject.en.en_US.fl_str_mv |
Leishmaniasis Drug-Related Side Effects and Adverse Reactions Parasites |
| topic |
Leishmaniasis Drug-Related Side Effects and Adverse Reactions Parasites Leishmaniasis Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos Parásitos Effets secondaires indésirables des médicaments Parasites Leishmania Leishmaniose Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos Parasitos |
| dc.subject.es.en_US.fl_str_mv |
Leishmaniasis Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos Parásitos |
| dc.subject.fr.en_US.fl_str_mv |
Effets secondaires indésirables des médicaments Parasites |
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Leishmania Leishmaniose Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos Parasitos |
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Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Londrina, PR, Brasil. |
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2023 |
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2023-05-16T19:47:39Z |
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2023-05-16T19:47:39Z |
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2023 |
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SCHIRMANN, Jéseka G. et al. In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphenyl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential. Scientific Reports, v. 17, p. 1-11, 2023. |
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https://www.arca.fiocruz.br/handle/icict/58450 |
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2045-2322 |
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https://doi.org/10.1038/s41598-023-34124-9 |
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SCHIRMANN, Jéseka G. et al. In‑vitro biological evaluation of 3,3′,5,5′‑tetramethoxy‑biphenyl‑4,4′‑diol and molecular docking studies on trypanothione reductase and Gp63 from Leishmania amazonensis demonstrated anti‑leishmania potential. Scientific Reports, v. 17, p. 1-11, 2023. 2045-2322 |
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Nature Research |
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Nature Research |
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