A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2019 |
| 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/40934 |
Resumo: | Universidade Federal de Mato Grosso do Sul. Instituto de Biociências. Laboratório de Parasitologia Humana. Campo Grande, MS, Brasil. |
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Arruda, Carla Cardozo Pinto deHardoim, Daiana de JesusRizk, Yasmin SilvaSouza, Celeste da Silva Freitas deValle, Tânia Zaverucha doCarvalho, Diego BentoTaniwaki, Noemi NosomiBaroni, Adriano Cesar de MoraisCalabrese, Kátia da Silva2020-04-23T14:56:55Z2020-04-23T14:56:55Z2019ARRUDA, Carla Cardoso Pinto de et al. A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction. Molecules, v. 25, n. 1, p. 1-13, 20 Dec. 2019.1420-3049https://www.arca.fiocruz.br/handle/icict/4093410.3390/molecules25010037engMDPILeishmania amazonensisDerivado sintéticoAtividade antileishmanialMorte celularUltraestruturaLeishmania amazonensisSynthetic derivativeAntileishmanial ActivityCell deathUltrastructureA triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunctioninfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal de Mato Grosso do Sul. Instituto de Biociências. Laboratório de Parasitologia Humana. Campo Grande, MS, 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.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.Universidade Federal de Mato Grosso do Sul. Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição. Laboratório de Síntese e Química Medicinal. Campo Grande, MS, Brasil.Instituto Adolfo Lutz. Núcleo de Microscopia Eletrônica. São Paulo, SP, Brasil.Universidade Federal de Mato Grosso do Sul. Faculdade de Ciências Farmacêuticas, Alimentos e Nutrição. Laboratório de Síntese e Química Medicinal. Campo Grande, MS, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil.In the search for new compounds with antileishmanial activity, we synthesized a triazole hybrid analogue of the neolignans grandisin and machilin G (LASQUIM 25), which was previously found highly active against both promastigotes and intracellular amastigote forms of Leishmania amazonensis. In this work, we investigated the leishmanicidal effects of LASQUIM 25 to identify the mechanisms involved in the cell death of L. amazonensis promastigotes. Transmission electron microscopy (TEM) analysis showed marked effects of LASQUIM 25 (IC50 = 7.2 µM) on the morphology of promastigote forms, notably on mitochondria. The direct action of the triazole derivative on the parasite was noticed over time from 2 h to 48 h, and cells displayed several ultrastructural alterations characteristic of apoptotic cells. Also, flow cytometric analysis (FACS) after TMRE staining detected changes in mitochondrial membrane potential after LASQUIM 25 treatment (64.83% labeling versus 83.38% labeling in nontreated cells). On the other hand, FACS after PI staining in 24 h-treatment showed a slight alteration in the integrity of the cell membrane, a necrotic event (16.76% necrotic cells versus 3.19% staining in live parasites). An abnormal secretion of lipids was observed, suggesting an exocytic activity. Another striking finding was the presence of autophagy-related lysosome-like vacuoles, suggesting an autophagic cell death that may arise as consequence of mitochondrial stress. Taken together, these results suggest that LASQUIM 25 leishmanicidal mechanisms involve some degree of mitochondrial dysregulation, already evidenced by the treatment with the IC50 of this compound. This effect may be due to the presence of a methylenedioxy group originated from machilin G, whose toxicity has been associated with the capacity to generate electrophilic intermediates.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/40934/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALKatiaCalabrese_DaianaHardoim_etal_IOC_2019.pdfKatiaCalabrese_DaianaHardoim_etal_IOC_2019.pdfapplication/pdf3534066https://www.arca.fiocruz.br/bitstream/icict/40934/2/KatiaCalabrese_DaianaHardoim_etal_IOC_2019.pdf7844ff51f5a0ee6943542bc18bc01443MD52TEXTKatiaCalabrese_DaianaHardoim_etal_IOC_2019.pdf.txtKatiaCalabrese_DaianaHardoim_etal_IOC_2019.pdf.txtExtracted 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| dc.title.en.fl_str_mv |
A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction |
| title |
A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction |
| spellingShingle |
A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction Arruda, Carla Cardozo Pinto de Leishmania amazonensis Derivado sintético Atividade antileishmanial Morte celular Ultraestrutura Leishmania amazonensis Synthetic derivative Antileishmanial Activity Cell death Ultrastructure |
| title_short |
A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction |
| title_full |
A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction |
| title_fullStr |
A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction |
| title_full_unstemmed |
A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction |
| title_sort |
A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction |
| author |
Arruda, Carla Cardozo Pinto de |
| author_facet |
Arruda, Carla Cardozo Pinto de Hardoim, Daiana de Jesus Rizk, Yasmin Silva Souza, Celeste da Silva Freitas de Valle, Tânia Zaverucha do Carvalho, Diego Bento Taniwaki, Noemi Nosomi Baroni, Adriano Cesar de Morais Calabrese, Kátia da Silva |
| author_role |
author |
| author2 |
Hardoim, Daiana de Jesus Rizk, Yasmin Silva Souza, Celeste da Silva Freitas de Valle, Tânia Zaverucha do Carvalho, Diego Bento Taniwaki, Noemi Nosomi Baroni, Adriano Cesar de Morais Calabrese, Kátia da Silva |
| author2_role |
author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Arruda, Carla Cardozo Pinto de Hardoim, Daiana de Jesus Rizk, Yasmin Silva Souza, Celeste da Silva Freitas de Valle, Tânia Zaverucha do Carvalho, Diego Bento Taniwaki, Noemi Nosomi Baroni, Adriano Cesar de Morais Calabrese, Kátia da Silva |
| dc.subject.other.pt_BR.fl_str_mv |
Leishmania amazonensis Derivado sintético Atividade antileishmanial Morte celular Ultraestrutura |
| topic |
Leishmania amazonensis Derivado sintético Atividade antileishmanial Morte celular Ultraestrutura Leishmania amazonensis Synthetic derivative Antileishmanial Activity Cell death Ultrastructure |
| dc.subject.en.pt_BR.fl_str_mv |
Leishmania amazonensis Synthetic derivative Antileishmanial Activity Cell death Ultrastructure |
| description |
Universidade Federal de Mato Grosso do Sul. Instituto de Biociências. Laboratório de Parasitologia Humana. Campo Grande, MS, Brasil. |
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2019 |
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2019 |
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2020-04-23T14:56:55Z |
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2020-04-23T14:56:55Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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ARRUDA, Carla Cardoso Pinto de et al. A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction. Molecules, v. 25, n. 1, p. 1-13, 20 Dec. 2019. |
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https://www.arca.fiocruz.br/handle/icict/40934 |
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1420-3049 |
| dc.identifier.doi.pt_BR.fl_str_mv |
10.3390/molecules25010037 |
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ARRUDA, Carla Cardoso Pinto de et al. A triazole hybrid of neolignans as a potential antileishmanial agent by triggering mitochondrial dysfunction. Molecules, v. 25, n. 1, p. 1-13, 20 Dec. 2019. 1420-3049 10.3390/molecules25010037 |
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