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 Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10362/121167 |
Resumo: | Funding Information: This research was funded by the Coordination for the Improvement of Higher Education Personnel (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior do Brazil; CAPES) grant number Finance Code 001; and the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro; FAPERJ) grant number E-26/010.001759/2019. The APC was funded by the Oswaldo Cruz Institute (Instituto Oswaldo Cruz; IOC). Dr. Fernando Almeida-Souza is a postdoctoral researcher fellow of CAPES grant number 88887.363006/2019-00. Dra. Ana Lucia Abreu-Silva is a research productivity fellow of National Scientific and Technological Development Council (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; CNPq) grant number 309885/2017-5. |
| id |
RCAP_b492ac120296cbf4cefe4473d92cd972 |
|---|---|
| oai_identifier_str |
oai:run.unl.pt:10362/121167 |
| network_acronym_str |
RCAP |
| network_name_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository_id_str |
7160 |
| spelling |
1,4-disubstituted-1,2,3-triazole compounds induce ultrastructural alterations in leishmania amazonensis promastigote: An in vitro antileishmanial and in silico pharmacokinetic studyADMECytotoxicityLeishmaniasisToxicityTransmission electron microscopyTreatmentCatalysisMolecular BiologySpectroscopyComputer Science ApplicationsPhysical and Theoretical ChemistryOrganic ChemistryInorganic ChemistryFunding Information: This research was funded by the Coordination for the Improvement of Higher Education Personnel (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior do Brazil; CAPES) grant number Finance Code 001; and the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro; FAPERJ) grant number E-26/010.001759/2019. The APC was funded by the Oswaldo Cruz Institute (Instituto Oswaldo Cruz; IOC). Dr. Fernando Almeida-Souza is a postdoctoral researcher fellow of CAPES grant number 88887.363006/2019-00. Dra. Ana Lucia Abreu-Silva is a research productivity fellow of National Scientific and Technological Development Council (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; CNPq) grant number 309885/2017-5.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.DQ - Departamento de QuímicaRUNAlmeida-Souza, Fernandoda Silva, Verônica DinizSilva, Gabriel XavierTaniwaki, Noemi NosomiHardoim, Daiana de JesusBuarque, Camilla DjenneAbreu-Silva, Ana LuciaCalabrese, Kátia da Silva2021-07-16T22:21:42Z2020-09-022020-09-02T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/article20application/pdfhttp://hdl.handle.net/10362/121167eng1661-6596PURE: 32601448https://doi.org/10.3390/ijms21186839info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2024-03-11T05:03:29Zoai:run.unl.pt:10362/121167Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-20T03:44:32.434963Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.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 Almeida-Souza, Fernando ADME Cytotoxicity Leishmaniasis Toxicity Transmission electron microscopy Treatment Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry |
| 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 |
Almeida-Souza, Fernando |
| author_facet |
Almeida-Souza, Fernando da Silva, Verônica Diniz Silva, Gabriel Xavier Taniwaki, Noemi Nosomi Hardoim, Daiana de Jesus Buarque, Camilla Djenne Abreu-Silva, Ana Lucia Calabrese, Kátia da Silva |
| author_role |
author |
| author2 |
da Silva, Verônica Diniz Silva, Gabriel Xavier Taniwaki, Noemi Nosomi Hardoim, Daiana de Jesus Buarque, Camilla Djenne Abreu-Silva, Ana Lucia Calabrese, Kátia da Silva |
| author2_role |
author author author author author author author |
| dc.contributor.none.fl_str_mv |
DQ - Departamento de Química RUN |
| dc.contributor.author.fl_str_mv |
Almeida-Souza, Fernando da Silva, Verônica Diniz Silva, Gabriel Xavier Taniwaki, Noemi Nosomi Hardoim, Daiana de Jesus Buarque, Camilla Djenne Abreu-Silva, Ana Lucia Calabrese, Kátia da Silva |
| dc.subject.por.fl_str_mv |
ADME Cytotoxicity Leishmaniasis Toxicity Transmission electron microscopy Treatment Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry |
| topic |
ADME Cytotoxicity Leishmaniasis Toxicity Transmission electron microscopy Treatment Catalysis Molecular Biology Spectroscopy Computer Science Applications Physical and Theoretical Chemistry Organic Chemistry Inorganic Chemistry |
| description |
Funding Information: This research was funded by the Coordination for the Improvement of Higher Education Personnel (Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior do Brazil; CAPES) grant number Finance Code 001; and the Carlos Chagas Filho Foundation for Research Support of the State of Rio de Janeiro (Fundacao Carlos Chagas Filho de Amparo a Pesquisa do Estado do Rio de Janeiro; FAPERJ) grant number E-26/010.001759/2019. The APC was funded by the Oswaldo Cruz Institute (Instituto Oswaldo Cruz; IOC). Dr. Fernando Almeida-Souza is a postdoctoral researcher fellow of CAPES grant number 88887.363006/2019-00. Dra. Ana Lucia Abreu-Silva is a research productivity fellow of National Scientific and Technological Development Council (Conselho Nacional de Desenvolvimento Cientifico e Tecnologico; CNPq) grant number 309885/2017-5. |
| publishDate |
2020 |
| dc.date.none.fl_str_mv |
2020-09-02 2020-09-02T00:00:00Z 2021-07-16T22:21:42Z |
| dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
| dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10362/121167 |
| url |
http://hdl.handle.net/10362/121167 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
1661-6596 PURE: 32601448 https://doi.org/10.3390/ijms21186839 |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.format.none.fl_str_mv |
20 application/pdf |
| dc.source.none.fl_str_mv |
reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
| instname_str |
Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| instacron_str |
RCAAP |
| institution |
RCAAP |
| reponame_str |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| collection |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| repository.name.fl_str_mv |
Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
| repository.mail.fl_str_mv |
|
| _version_ |
1799138053239865344 |