Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B

Detalhes bibliográficos
Autor(a) principal: Branquinha, Marta H.
Data de Publicação: 2022
Outros Autores: Araújo, Pedro S. S., Oliveira, Simone S. C., Sangenito, Leandro S., Gonçalves, Diego S., Seabra, Sergio H., d`Avila-Levy, Claudia M., Santos, André L.S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/52001
Resumo: Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil.
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spelling Branquinha, Marta H.Araújo, Pedro S. S.Oliveira, Simone S. C.Sangenito, Leandro S.Gonçalves, Diego S.Seabra, Sergio H.d`Avila-Levy, Claudia M.Santos, André L.S.2022-04-03T18:53:06Z2022-04-03T18:53:06Z2022BRANQUINHA, Marta H. et al. Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B. Tropical Medicine and Infectious Disease, v. 7, n. 29, p. 1 - 15, Feb. 2022.2414-6366https://www.arca.fiocruz.br/handle/icict/5200110.3390/tropicalmed 7020029engMDPILeishmanioseQuimioterapiaMDL28170Anfotericina BLeishmaniasisChemotherapyMDL28170Amphotericin BAntileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin Binfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Pós-Graduação em Bioquímica,. Rio de Janeiro, RJ, Brasil.Universidade Estadual do Norte Fluminense Darcy Ribeiro. Centro de Biociências e Biotecnologia. Laboratório de Biologia Celular e Tecidual. Campos dos Goytacases, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Estudos Integrados em Protozoologia. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil / Universidade Federal do Rio de Janeiro. Instituto de Química. Programa de Pós-Graduação em Bioquímica,. Rio de Janeiro, RJ, Brasil.The necessity of drug combinations to treat leishmaniasis came to the surface mainly because of the toxicity of current treatments and the emergence of resistant strains. The calpain inhibitor MDL28170 has previously shown anti-Leishmania activity, therefore its use in association with standard drugs could provide a new alternative for the treatment strategy against leishmaniasis. In this study, we analyzed the potential of the combination of MDL28170 and the antileishmanial drug amphotericin B against Leishmania amazonensis and Leishmania chagasi. The compounds were tested in the combination of the 1/2 IC50 value of MDL28170 plus the 1/4 IC50 value of amphotericin B, which led to an increment in the anti-promastigote activity when compared to the single drug treatments. This drug association revealed several and severe morphophysiological changes on parasite cells, such as loss of plasma membrane integrity, reduced size of flagellum, and depolarization of mitochondrial membrane potential besides increased reactive oxygen species production. In addition, the combination of both drugs had a deleterious effect on the Leishmania–macrophage interaction, reflecting in a significant anti-amastigote action, which achieved a reduction of 50% in the association index. These results indicate that the combination treatment proposed here may represent a new alternative for leishmaniasis chemotherapy.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/52001/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALMartaBranquinha_ClaudiaLevy_etal_IOC_2022.pdfMartaBranquinha_ClaudiaLevy_etal_IOC_2022.pdfapplication/pdf2947148https://www.arca.fiocruz.br/bitstream/icict/52001/2/MartaBranquinha_ClaudiaLevy_etal_IOC_2022.pdf6e88ca673c498e74d8d034fe8ea3cd2cMD52icict/520012022-06-24 12:59:52.537oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-06-24T15:59:52Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false
dc.title.pt_BR.fl_str_mv Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B
title Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B
spellingShingle Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B
Branquinha, Marta H.
Leishmaniose
Quimioterapia
MDL28170
Anfotericina B
Leishmaniasis
Chemotherapy
MDL28170
Amphotericin B
title_short Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B
title_full Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B
title_fullStr Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B
title_full_unstemmed Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B
title_sort Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B
author Branquinha, Marta H.
author_facet Branquinha, Marta H.
Araújo, Pedro S. S.
Oliveira, Simone S. C.
Sangenito, Leandro S.
Gonçalves, Diego S.
Seabra, Sergio H.
d`Avila-Levy, Claudia M.
Santos, André L.S.
author_role author
author2 Araújo, Pedro S. S.
Oliveira, Simone S. C.
Sangenito, Leandro S.
Gonçalves, Diego S.
Seabra, Sergio H.
d`Avila-Levy, Claudia M.
Santos, André L.S.
author2_role author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Branquinha, Marta H.
Araújo, Pedro S. S.
Oliveira, Simone S. C.
Sangenito, Leandro S.
Gonçalves, Diego S.
Seabra, Sergio H.
d`Avila-Levy, Claudia M.
Santos, André L.S.
dc.subject.other.pt_BR.fl_str_mv Leishmaniose
Quimioterapia
MDL28170
Anfotericina B
topic Leishmaniose
Quimioterapia
MDL28170
Anfotericina B
Leishmaniasis
Chemotherapy
MDL28170
Amphotericin B
dc.subject.en.pt_BR.fl_str_mv Leishmaniasis
Chemotherapy
MDL28170
Amphotericin B
description Universidade Federal do Rio de Janeiro. Instituto de Microbiologia Paulo de Góes. Departamento de Microbiologia Geral. Laboratório de Estudos Avançados de Microrganismos Emergentes e Resistentes. Rio de Janeiro, RJ, Brasil.
publishDate 2022
dc.date.accessioned.fl_str_mv 2022-04-03T18:53:06Z
dc.date.available.fl_str_mv 2022-04-03T18:53:06Z
dc.date.issued.fl_str_mv 2022
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.citation.fl_str_mv BRANQUINHA, Marta H. et al. Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B. Tropical Medicine and Infectious Disease, v. 7, n. 29, p. 1 - 15, Feb. 2022.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/52001
dc.identifier.issn.pt_BR.fl_str_mv 2414-6366
dc.identifier.doi.none.fl_str_mv 10.3390/tropicalmed 7020029
identifier_str_mv BRANQUINHA, Marta H. et al. Antileishmanial Efficacy of the Calpain Inhibitor MDL28170 in Combination with Amphotericin B. Tropical Medicine and Infectious Disease, v. 7, n. 29, p. 1 - 15, Feb. 2022.
2414-6366
10.3390/tropicalmed 7020029
url https://www.arca.fiocruz.br/handle/icict/52001
dc.language.iso.fl_str_mv eng
language eng
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.publisher.none.fl_str_mv MDPI
publisher.none.fl_str_mv MDPI
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
instname:Fundação Oswaldo Cruz (FIOCRUZ)
instacron:FIOCRUZ
instname_str Fundação Oswaldo Cruz (FIOCRUZ)
instacron_str FIOCRUZ
institution FIOCRUZ
reponame_str Repositório Institucional da FIOCRUZ (ARCA)
collection Repositório Institucional da FIOCRUZ (ARCA)
bitstream.url.fl_str_mv https://www.arca.fiocruz.br/bitstream/icict/52001/1/license.txt
https://www.arca.fiocruz.br/bitstream/icict/52001/2/MartaBranquinha_ClaudiaLevy_etal_IOC_2022.pdf
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repository.name.fl_str_mv Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)
repository.mail.fl_str_mv repositorio.arca@fiocruz.br
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