Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking
| Autor(a) principal: | |
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| Data de Publicação: | 2022 |
| 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/56455 |
Resumo: | Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil / Universidade de São Paulo. Instituto de Física de São Carlos. Laboratório de Química Medicinal e Computacional. São Carlos, SP, Brasil. |
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Silva, João Victor SilvaMoreira, Rosiane FernandesWatanabe, Luciano AlmeidaSouza, Celeste da Silva Freitas deHardoim, Daiana de JesusTaniwaki, Noemi NosomiBertho, Alvaro LuizTeixeira, Kerolain FaoroCenci, Arthur RibeiroDoring, Thiago HenriqueCruz Júnior, José Wilmo daOliveira, Aldo Sena deMarinho, Patrícia Santana BarbosaCalabrese, Kátia da SilvaMarinho, Andrey Moacir do RosarioSouza, Fernando Almeida2023-01-13T14:01:33Z2023-01-13T14:01:33Z2022SILVA, João Victor Silva et al. Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking. Frontiers in Cellular and Infection Microbiology, v. 12, 974910, p. 1 - 17, Aug. 2022.2235-2988https://www.arca.fiocruz.br/handle/icict/5645510.3389/fcimb.2022.974910engFrontiers MediaLeishmania amazonensisMonometilsulochrinaMicroscópio eletrônicoCitometria de fluxoPotencial de membrana mitocondrialCYP51ADMETMonomethylsulochrinLeishmania amazonensisElectron microscopyFlow cytometryMitochondrial membrane potentialCYP51ADMETMonomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular dockinginfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleFundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil / Universidade de São Paulo. Instituto de Física de São Carlos. Laboratório de Química Medicinal e Computacional. São Carlos, SP, Brasil.Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil.Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil.Instituto Adolpho Lutz. Centro de Microscopia Eletrônica. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Instalação Central de Citometria de Fluxo. Rio de Janeiro, RJ, Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ, Brasil.Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil.Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil.Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil.Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil.Universidade Federal de Santa Catarina. Departamento de Ciências Exatas e Educação. Blumenau, SC, Brasil.Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Pará. Programa de Pós-Graduação em Química. Belém, PA, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil / Universidade do Estado do Maranhão. Programa de Pós-Graduação em Ciências de Animais. São Luis, MA, Brasil.Leishmaniasis represents a serious world health problem, with 1 billion people being exposed to infection and a broad spectrum of clinical manifestations with a potentially fatal outcome. Based on the limitations observed in the treatment of leishmaniasis, such as high cost, significant adverse effects, and the potential for drug resistance, the aim of the present study was to evaluate the leishmanicidal activity of the compounds pseurotin A and monomethylsulochrin isolated from the biomass extract of Aspergillus sp. The chromatographic profiles of the extract were determined by high-performance liquid chromatography coupled with a diode-array UV-Vis detector (HPLC-DAD-UV), and the molecular identification of the pseurotin A and monomethylsulochrin were carried out by electrospray ionization mass spectrometry in tandem (LC-ESI-MS-MS) and nuclear magnetic resonance (NMR). Antileishmanial activity was assayed against promastigote and intracellular amastigote of Leishmania amazonensis. As a control, cytotoxicity assays were performed in non-infected BALB/c peritoneal macrophages. Ultrastructural alterations in parasites were evaluated by transmission electron microscopy. Changes in mitochondrial membrane potential were determined by flow cytometry. Only monomethylsulochrin inhibited the promastigote growth (IC50 18.04 ± 1.11 μM), with cytotoxicity to peritoneal macrophages (CC50 5.09 91.63 ± 1.28 μM). Activity against intracellular amastigote forms (IC50 5.09 ± 1.06 μM) revealed an increase in antileishmanial activity when compared with promastigotes. In addition to a statistically significant reduction in the evaluated infection parameters, monomethylsulochrin altered the ultrastructure of the promastigote forms with atypical vacuoles, electron-dense corpuscles in the cytoplasm, changes at the mitochondria outer membrane and abnormal disposition around the kinetoplast. It was showed that monomethylsulochrin leads to a decrease in the mitochondrial membrane potential (25.9%, p = 0.0286). Molecular modeling studies revealed that monomethylsulochrin can act as inhibitor of sterol 14-alpha-demethylase (CYP51), a therapeutic target for human trypanosomiasis and leishmaniasis. Assessed for its drug likeness, monomethylsulochrin follows the Lipinski Rule of five and Ghose, Veber, Egan, and Muegge criteria. Furthermore, monomethylsulochrin can be used as a reference in the development of novel and therapeutically useful antileishmanial agents.info: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/56455/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALAlvaroBerto_KatiaCalabrese_etal_IOC_2022.pdfAlvaroBerto_KatiaCalabrese_etal_IOC_2022.pdfapplication/pdf54776315https://www.arca.fiocruz.br/bitstream/icict/56455/2/AlvaroBerto_KatiaCalabrese_etal_IOC_2022.pdf186a015a50f273c4da1e6a0ee85700c3MD52icict/564552023-09-04 11:17:44.823oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352023-09-04T14:17:44Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.en_US.fl_str_mv |
Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking |
| title |
Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking |
| spellingShingle |
Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking Silva, João Victor Silva Leishmania amazonensis Monometilsulochrina Microscópio eletrônico Citometria de fluxo Potencial de membrana mitocondrial CYP51 ADMET Monomethylsulochrin Leishmania amazonensis Electron microscopy Flow cytometry Mitochondrial membrane potential CYP51 ADMET |
| title_short |
Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking |
| title_full |
Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking |
| title_fullStr |
Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking |
| title_full_unstemmed |
Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking |
| title_sort |
Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking |
| author |
Silva, João Victor Silva |
| author_facet |
Silva, João Victor Silva Moreira, Rosiane Fernandes Watanabe, Luciano Almeida Souza, Celeste da Silva Freitas de Hardoim, Daiana de Jesus Taniwaki, Noemi Nosomi Bertho, Alvaro Luiz Teixeira, Kerolain Faoro Cenci, Arthur Ribeiro Doring, Thiago Henrique Cruz Júnior, José Wilmo da Oliveira, Aldo Sena de Marinho, Patrícia Santana Barbosa Calabrese, Kátia da Silva Marinho, Andrey Moacir do Rosario Souza, Fernando Almeida |
| author_role |
author |
| author2 |
Moreira, Rosiane Fernandes Watanabe, Luciano Almeida Souza, Celeste da Silva Freitas de Hardoim, Daiana de Jesus Taniwaki, Noemi Nosomi Bertho, Alvaro Luiz Teixeira, Kerolain Faoro Cenci, Arthur Ribeiro Doring, Thiago Henrique Cruz Júnior, José Wilmo da Oliveira, Aldo Sena de Marinho, Patrícia Santana Barbosa Calabrese, Kátia da Silva Marinho, Andrey Moacir do Rosario Souza, Fernando Almeida |
| author2_role |
author author author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Silva, João Victor Silva Moreira, Rosiane Fernandes Watanabe, Luciano Almeida Souza, Celeste da Silva Freitas de Hardoim, Daiana de Jesus Taniwaki, Noemi Nosomi Bertho, Alvaro Luiz Teixeira, Kerolain Faoro Cenci, Arthur Ribeiro Doring, Thiago Henrique Cruz Júnior, José Wilmo da Oliveira, Aldo Sena de Marinho, Patrícia Santana Barbosa Calabrese, Kátia da Silva Marinho, Andrey Moacir do Rosario Souza, Fernando Almeida |
| dc.subject.other.en_US.fl_str_mv |
Leishmania amazonensis Monometilsulochrina Microscópio eletrônico Citometria de fluxo Potencial de membrana mitocondrial CYP51 ADMET |
| topic |
Leishmania amazonensis Monometilsulochrina Microscópio eletrônico Citometria de fluxo Potencial de membrana mitocondrial CYP51 ADMET Monomethylsulochrin Leishmania amazonensis Electron microscopy Flow cytometry Mitochondrial membrane potential CYP51 ADMET |
| dc.subject.en.en_US.fl_str_mv |
Monomethylsulochrin Leishmania amazonensis Electron microscopy Flow cytometry Mitochondrial membrane potential CYP51 ADMET |
| description |
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil / Universidade de São Paulo. Instituto de Física de São Carlos. Laboratório de Química Medicinal e Computacional. São Carlos, SP, Brasil. |
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2022 |
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2022 |
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2023-01-13T14:01:33Z |
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2023-01-13T14:01:33Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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SILVA, João Victor Silva et al. Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking. Frontiers in Cellular and Infection Microbiology, v. 12, 974910, p. 1 - 17, Aug. 2022. |
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https://www.arca.fiocruz.br/handle/icict/56455 |
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2235-2988 |
| dc.identifier.doi.none.fl_str_mv |
10.3389/fcimb.2022.974910 |
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SILVA, João Victor Silva et al. Monomethylsulochrin isolated from biomass extract of Aspergillus sp. against Leishmania amazonensis: In vitro biological evaluation and molecular docking. Frontiers in Cellular and Infection Microbiology, v. 12, 974910, p. 1 - 17, Aug. 2022. 2235-2988 10.3389/fcimb.2022.974910 |
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