1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2020 |
| 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/45479 |
Resumo: | Universidade Estadual do Maranhão. Pós-graduação em Ciência Animal. São Luis, MA. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz, Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. |
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Souza, Fernando AlmeidaSilva, Verônica Diniz daSilva, Gabriel XavierTaniwaki, Noemi NosomiHardoim, Daiana de JesusBuarque, Camila DjenneSilva, Ana Lucia AbreuCalabrese, Kátia da Silva2020-12-30T18:24:50Z2020-12-30T18:24:50Z2020SOUZA, Fernando Almeida et al. 1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study. International Journal of Molecular Sciences, v. 21, n. 16, p. 1-20, Sept. 2020.1661-6596https://www.arca.fiocruz.br/handle/icict/4547910.3390/ijms211868391433-6596engMDPICitotoxicidadeMicroscopia eletrônica de transmissãoLeishmanioseTratamentoToxicidadeCytotoxicityTransmission electron microscopyLeishmaniasisTreatmentADMEToxicity1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Studyinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Estadual do Maranhão. Pós-graduação em Ciência Animal. São Luis, MA. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz, Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil.Pontifícia Universidade Católica. Laboratório de Síntese Orgânica. Rio de Janeiro, RJ, Brasil / Universidade Nova de Lisboa. Faculdade de Ciência e Tecnologia. Caparica, Portugal.Universidade Federal do Maranhão. Rede Nordeste de Biotecnologia. São Luis, MA, Brasil.Instituto Adolfo Lutz. Núcleo de Microscopia Eletrônica. São Paulo, SP, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz, Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil.Pontifícia Universidade Católica. Laboratório de Síntese Orgânica. Rio de Janeiro, RJ, Brasil.Universidade Estadual do Maranhão. Pós-graduação em Ciência Animal. São Luis, MA. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz, Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil.The current standard treatment for leishmaniasis has remained the same for over 100 years, despite inducing several adverse effects and increasing cases of resistance. In this study we evaluated the in vitro antileishmanial activity of 1,4-disubstituted-1,2,3 triazole compounds and carried out in silico predictive study of their pharmacokinetic and toxicity properties. Ten compounds were analyzed, with compound 6 notably presenting IC50: 14.64 ± 4.392 µM against promastigotes, IC50: 17.78 ± 3.257 µM against intracellular amastigotes, CC50: 547.88 ± 3.256 µM against BALB/c peritoneal macrophages, and 30.81-fold selectivity for the parasite over the cells. It also resulted in a remarkable decrease in all the parameters of in vitro infection. Ultrastructural analysis revealed lipid corpuscles, a nucleus with discontinuity of the nuclear membrane, a change in nuclear chromatin, and kinetoplast swelling with breakdown of the mitochondrial cristae and electron-density loss induced by 1,4-disubstituted-1,2,3-triazole treatment. In addition, compound 6 enhanced 2.3-fold the nitrite levels in the Leishmania-stimulated macrophages. In silico pharmacokinetic prediction of compound 6 revealed that it is not recommended for topical formulation cutaneous leishmaniasis treatment, however the other properties exhibited results that were similar or even better than miltefosine, making it a good candidate for further in vivo studies against Leishmania parasites.18info: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/45479/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALFernandoSouza_DaianaHardoim_etal_IOC_2020.pdfFernandoSouza_DaianaHardoim_etal_IOC_2020.pdfapplication/pdf8986239https://www.arca.fiocruz.br/bitstream/icict/45479/2/FernandoSouza_DaianaHardoim_etal_IOC_2020.pdf061c158625dab967fa2c1668da4a40d8MD52TEXTFernandoSouza_DaianaHardoim_etal_IOC_2020.pdf.txtFernandoSouza_DaianaHardoim_etal_IOC_2020.pdf.txtExtracted 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| dc.title.pt_BR.fl_str_mv |
1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study |
| title |
1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study |
| spellingShingle |
1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study Souza, Fernando Almeida Citotoxicidade Microscopia eletrônica de transmissão Leishmaniose Tratamento Toxicidade Cytotoxicity Transmission electron microscopy Leishmaniasis Treatment ADME Toxicity |
| title_short |
1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study |
| title_full |
1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study |
| title_fullStr |
1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study |
| title_full_unstemmed |
1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study |
| title_sort |
1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study |
| author |
Souza, Fernando Almeida |
| author_facet |
Souza, Fernando Almeida Silva, Verônica Diniz da Silva, Gabriel Xavier Taniwaki, Noemi Nosomi Hardoim, Daiana de Jesus Buarque, Camila Djenne Silva, Ana Lucia Abreu Calabrese, Kátia da Silva |
| author_role |
author |
| author2 |
Silva, Verônica Diniz da Silva, Gabriel Xavier Taniwaki, Noemi Nosomi Hardoim, Daiana de Jesus Buarque, Camila Djenne Silva, Ana Lucia Abreu Calabrese, Kátia da Silva |
| author2_role |
author author author author author author author |
| dc.contributor.author.fl_str_mv |
Souza, Fernando Almeida Silva, Verônica Diniz da Silva, Gabriel Xavier Taniwaki, Noemi Nosomi Hardoim, Daiana de Jesus Buarque, Camila Djenne Silva, Ana Lucia Abreu Calabrese, Kátia da Silva |
| dc.subject.other.pt_BR.fl_str_mv |
Citotoxicidade Microscopia eletrônica de transmissão Leishmaniose Tratamento Toxicidade |
| topic |
Citotoxicidade Microscopia eletrônica de transmissão Leishmaniose Tratamento Toxicidade Cytotoxicity Transmission electron microscopy Leishmaniasis Treatment ADME Toxicity |
| dc.subject.en.pt_BR.fl_str_mv |
Cytotoxicity Transmission electron microscopy Leishmaniasis Treatment ADME Toxicity |
| description |
Universidade Estadual do Maranhão. Pós-graduação em Ciência Animal. São Luis, MA. Brasil / Fundação Oswaldo Cruz. Instituto Oswaldo Cruz, Laboratório de Imunomodulação e Protozoologia. Rio de Janeiro, RJ, Brasil. |
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2020 |
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2020-12-30T18:24:50Z |
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2020-12-30T18:24:50Z |
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2020 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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SOUZA, Fernando Almeida et al. 1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study. International Journal of Molecular Sciences, v. 21, n. 16, p. 1-20, Sept. 2020. |
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https://www.arca.fiocruz.br/handle/icict/45479 |
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1661-6596 |
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10.3390/ijms21186839 |
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1433-6596 |
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SOUZA, Fernando Almeida et al. 1,4-Disubstituted-1,2,3-Triazole Compounds Induce Ultrastructural Alterations in Leishmania amazonensis Promastigote: An in Vitro Antileishmanial and in Silico Pharmacokinetic Study. International Journal of Molecular Sciences, v. 21, n. 16, p. 1-20, Sept. 2020. 1661-6596 10.3390/ijms21186839 1433-6596 |
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