Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2021 |
| 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/50071 |
Resumo: | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Programa de Pós-Graduação em Biociências e Biotecnologia. Curitiba, PR, Brasil. / Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil. |
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Bortoleti, Bruna Taciane da SilvaGonçalves, Manoela DaieleTomiotto-Pellissier, FernandaCamargo, Priscila GoesAssolini, João PauloConcato, Virgínia MárciaDetoni, Mariana BarbosaBidóia, Danielle LarazinBispo, Marcelle de Lima FerreiraLima, Camilo Henrique da SilvaMacedo Junior, Fernando Cesar deConchon-Costa, IveteMiranda-Sapla, Milena MenegazzoWowk, Pryscilla FaniniPavanelli, Wander Rogério2021-11-26T11:45:46Z2021-11-26T11:45:46Z2022BORTOLETI, Bruna Taciane da Silva et al. Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins. Chemico-Biological Interactions. v. 351, n. 109690, p. 1–15, 2022.0009-2797https://www.arca.fiocruz.br/handle/icict/5007110.1016/j.cbi.2021.109690porElsevier. International Society for the Study of XenobioticsInvestigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoinsinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Carlos Chagas. Programa de Pós-Graduação em Biociências e Biotecnologia. Curitiba, PR, Brasil. / Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil.Universidade Estadual de londrina. Laboratório de Biotransformação e Fitoquímica. Londrina, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Programa de Pós-Graduação em Biociências e Biotecnologia. Curitiba, PR, Brasil. / Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil.Universidade Estadual de londrina. Laboratório de Pesquisa em Moléculas Bioativas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Laboratório de Síntese de Moléculas Medicinais. Londrina, PR, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Universidade Estadual de londrina. Laboratório de Pesquisa em Moléculas Bioativas. Londrina, PR, Brasil.Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil.Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil.Fundação Oswaldo Cruz. Instituto Carlos Chagas. Curitiba, PR, Brasil.Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil.The currently available treatment options for leishmaniasis are associated with high costs, severe side effects, and high toxicity. In previous studies, thiohydantoins demonstrated some harmacological activities and were shown to be potential hit compounds with antileishmanial properties. The present study further explored the antileishmanial effect of acetyl-thiohydantoins against Leishmania amazonensis and determined the main processes involved in parasite death. We observed that compared to thiohydantoin nuclei, acetyl-thiohydantoin treatment inhibited the proliferation of promastigotes. This treatment caused alterations in cell cycle progression and parasite size and caused morphological and ultrastructural changes. We then investigated the mechanisms involved in the death of the protozoan; there was an increase in ROS production, phosphatidylserine exposure, and plasma membrane permeabilization and a loss of mitochondrial membrane potential, resulting in an accumulation of lipid bodies and the formation of autophagic vacuoles on these parasites and confirming an apoptosis-like process. In intracellular amastigotes, selected acetyl-thiohydantoins reduced the percentage of infected macrophages and the number of amastigotes/macrophages by increasing ROS production and reducing TNF-α levels. Moreover, thiohydantoins did not induce cytotoxicity in murine macrophages (J774A.1), human monocytes (THP-1), or sheep erythrocytes. In silico and in vitro analyses showed that acetyl-thiohydantoins exerted in vitro antileishmanial effects on L. amazonensis promastigotes in apoptosis-like and amastigote forms by inducing ROS production and reducing TNF-α levels, indicating that they are good candidates for drug discovery studies in leishmaniasis treatment. Additionally, we carried out molecular docking analyses of acetyl-thiohydantoins on two important targets of Leishmania amazonensis: arginase and TNF-alpha converting enzyme. The results suggested that the acetyl groups in the N1-position of the thiohydantoin ring and the ring itself could be pharmacophoric groups due to their affinity for binding amino acid residues at the active site of both enzymes via hydrogen bond interactions. These results demonstrate that thiohydantoins are promising hit compounds that could be used as antileishmanial agents.Apoptosis-likeThiohydantoinsMolecular Docking SimulationApoptosisTiohidantoínasSimulación del Acoplamiento MolecularApoptoseThiohydantoïnesSimulation de docking moléculaireApoptoseTioidantoínasSimulação de Acoplamento MolecularLeishmaniainfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-83084https://www.arca.fiocruz.br/bitstream/icict/50071/1/license.txt783568c2893d2e25a99990b126be1772MD51ORIGINAL1-s2.0-S0009279721003288-OK.pdf1-s2.0-S0009279721003288-OK.pdfapplication/pdf16546253https://www.arca.fiocruz.br/bitstream/icict/50071/2/1-s2.0-S0009279721003288-OK.pdf0e4b22e9c7cf6d9ad9354ee889030282MD52icict/500712021-12-23 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| dc.title.pt_BR.fl_str_mv |
Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins |
| title |
Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins |
| spellingShingle |
Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins Bortoleti, Bruna Taciane da Silva Apoptosis-like Thiohydantoins Molecular Docking Simulation Apoptosis Tiohidantoínas Simulación del Acoplamiento Molecular Apoptose Thiohydantoïnes Simulation de docking moléculaire Apoptose Tioidantoínas Simulação de Acoplamento Molecular Leishmania |
| title_short |
Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins |
| title_full |
Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins |
| title_fullStr |
Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins |
| title_full_unstemmed |
Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins |
| title_sort |
Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins |
| author |
Bortoleti, Bruna Taciane da Silva |
| author_facet |
Bortoleti, Bruna Taciane da Silva Gonçalves, Manoela Daiele Tomiotto-Pellissier, Fernanda Camargo, Priscila Goes Assolini, João Paulo Concato, Virgínia Márcia Detoni, Mariana Barbosa Bidóia, Danielle Larazin Bispo, Marcelle de Lima Ferreira Lima, Camilo Henrique da Silva Macedo Junior, Fernando Cesar de Conchon-Costa, Ivete Miranda-Sapla, Milena Menegazzo Wowk, Pryscilla Fanini Pavanelli, Wander Rogério |
| author_role |
author |
| author2 |
Gonçalves, Manoela Daiele Tomiotto-Pellissier, Fernanda Camargo, Priscila Goes Assolini, João Paulo Concato, Virgínia Márcia Detoni, Mariana Barbosa Bidóia, Danielle Larazin Bispo, Marcelle de Lima Ferreira Lima, Camilo Henrique da Silva Macedo Junior, Fernando Cesar de Conchon-Costa, Ivete Miranda-Sapla, Milena Menegazzo Wowk, Pryscilla Fanini Pavanelli, Wander Rogério |
| author2_role |
author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Bortoleti, Bruna Taciane da Silva Gonçalves, Manoela Daiele Tomiotto-Pellissier, Fernanda Camargo, Priscila Goes Assolini, João Paulo Concato, Virgínia Márcia Detoni, Mariana Barbosa Bidóia, Danielle Larazin Bispo, Marcelle de Lima Ferreira Lima, Camilo Henrique da Silva Macedo Junior, Fernando Cesar de Conchon-Costa, Ivete Miranda-Sapla, Milena Menegazzo Wowk, Pryscilla Fanini Pavanelli, Wander Rogério |
| dc.subject.en.pt_BR.fl_str_mv |
Apoptosis-like Thiohydantoins Molecular Docking Simulation |
| topic |
Apoptosis-like Thiohydantoins Molecular Docking Simulation Apoptosis Tiohidantoínas Simulación del Acoplamiento Molecular Apoptose Thiohydantoïnes Simulation de docking moléculaire Apoptose Tioidantoínas Simulação de Acoplamento Molecular Leishmania |
| dc.subject.es.pt_BR.fl_str_mv |
Apoptosis Tiohidantoínas Simulación del Acoplamiento Molecular |
| dc.subject.fr.pt_BR.fl_str_mv |
Apoptose Thiohydantoïnes Simulation de docking moléculaire |
| dc.subject.decs.pt_BR.fl_str_mv |
Apoptose Tioidantoínas Simulação de Acoplamento Molecular Leishmania |
| description |
Fundação Oswaldo Cruz. Instituto Carlos Chagas. Programa de Pós-Graduação em Biociências e Biotecnologia. Curitiba, PR, Brasil. / Universidade Estadual de Londrina. Laboratório de Imunoparasitologia. Londrina, PR, Brasil. |
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2021 |
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2021-11-26T11:45:46Z |
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2021-11-26T11:45:46Z |
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2022 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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BORTOLETI, Bruna Taciane da Silva et al. Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins. Chemico-Biological Interactions. v. 351, n. 109690, p. 1–15, 2022. |
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https://www.arca.fiocruz.br/handle/icict/50071 |
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0009-2797 |
| dc.identifier.doi.none.fl_str_mv |
10.1016/j.cbi.2021.109690 |
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BORTOLETI, Bruna Taciane da Silva et al. Investigation of the antileishmanial activity and mechanisms of action of acetyl-thiohydantoins. Chemico-Biological Interactions. v. 351, n. 109690, p. 1–15, 2022. 0009-2797 10.1016/j.cbi.2021.109690 |
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Elsevier. International Society for the Study of Xenobiotics |
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Elsevier. International Society for the Study of Xenobiotics |
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