Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B

Detalhes bibliográficos
Autor(a) principal: Velásquez, Angela Maria Arenas
Data de Publicação: 2017
Outros Autores: Ribeiro, Willian Campos, Venn, Vutey, Castelli, Silvia, Camargo, Mariana Santoro de, Assis, Renata Pires de, Souza, Rodrigo Alves de, Ribeiro, Aline Rimoldi, Passalacqua, Thaís Gaban, Rosa, João Aristeu da, Baviera, Amanda Martins, Mauro, Antonio Eduardo, Desideri, Alessandro, Amaral, Elmo Eduardo Almeida, Graminha, Marcia A. S.
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da FIOCRUZ (ARCA)
Texto Completo: https://www.arca.fiocruz.br/handle/icict/26681
Resumo: Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil / Universidade do Estado de São Paulo. Instituto de Química. Araraquara, SP, Brasil.
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spelling Velásquez, Angela Maria ArenasRibeiro, Willian CamposVenn, VuteyCastelli, SilviaCamargo, Mariana Santoro deAssis, Renata Pires deSouza, Rodrigo Alves deRibeiro, Aline RimoldiPassalacqua, Thaís GabanRosa, João Aristeu daBaviera, Amanda MartinsMauro, Antonio EduardoDesideri, AlessandroAmaral, Elmo Eduardo AlmeidaGraminha, Marcia A. S.2018-05-30T12:07:03Z2018-05-30T12:07:03Z2017VELÀSQUEZ, Angela Maria Arenas; et al. Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B. Antimicrobial Agents and Chemotherapy, v.61, n.8, e00688-17, 15p, Aug. 2017.0066-4804https://www.arca.fiocruz.br/handle/icict/2668110.1128/AAC.00688-171098-6596engAmerican Society for MicrobiologyLeishmania amazonensisTrypanosoma cruzitopoisomerase 1BLeishmaniosecomplexo ciclopaladadoDoença de Chagascyclopalladated complexleishmaniasisChagas DiseaseLeishmania amazonensisTrypanosoma cruziLeishmania donovanitopoisomerase 1BEfficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1Binfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil / Universidade do Estado de São Paulo. Instituto de Química. Araraquara, SP, Brasil.Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil.University of Rome. TorVergata, Rome, Italy.University of Rome. TorVergata, Rome, Italy.University of Rome. TorVergata, Rome, Italy.Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil.Universidade do Estado de São Paulo. Instituto de Química. Araraquara, SP, Brasil.Universidade Estadual de Campinas. Instituto de Biologia. Campinas, SP, Brasil.Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil / Universidade Estadual de São Paulo. Instituto de Químca. Araraquara, SP, Brasil.Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil.Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil.Universidade do Estado de São Paulo. Instituto de Química. Araraquara, SP, Brasil.University of Rome. TorVergata, Rome, Italy..Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil.Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil.Leishmaniasis is a disease found throughout the (sub)tropical parts of the world caused by protozoan parasites of the Leishmania genus. Despite the numerous problems associated with existing treatments, pharmaceutical companies continue to neglect the development of better ones. The high toxicity of current drugs combined with emerging resistance makes the discovery of new therapeutic alternatives urgent. We report here the evaluation of a binuclear cyclopalladated complex containing Pd(II) and N,N'-dimethylbenzylamine (Hdmba) against Leishmania amazonensis The compound [Pd(dmba)(μ-N3)]2 (CP2) inhibits promastigote growth (50% inhibitory concentration [IC50] = 13.2 ± 0.7 μM) and decreases the proliferation of intracellular amastigotes in in vitro incubated macrophages (IC50 = 10.2 ± 2.2 μM) without a cytotoxic effect when tested against peritoneal macrophages (50% cytotoxic concentration = 506.0 ± 10.7 μM). In addition, CP2 was also active against T. cruzi intracellular amastigotes (IC50 = 2.3 ± 0.5 μM, selective index = 225), an indication of its potential for use in Chagas disease therapy. In vivo assays using L. amazonensis-infected BALB/c showed an 80% reduction in parasite load compared to infected and nontreated animals. Also, compared to amphotericin B treatment, CP2 did not show any side effects, which was corroborated by the analysis of plasma levels of different hepatic and renal biomarkers. Furthermore, CP2 was able to inhibit Leishmania donovani topoisomerase 1B (Ldtopo1B), a potentially important target in this parasite. (This study has been registered at ClinicalTrials.gov under identifier NCT02169141.).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/26681/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALelmo_amaral_etal_IOC_2017.pdfelmo_amaral_etal_IOC_2017.pdfapplication/pdf1249508https://www.arca.fiocruz.br/bitstream/icict/26681/2/elmo_amaral_etal_IOC_2017.pdf02577de795abd5559d0181f9b44fe388MD52TEXTelmo_amaral_etal_IOC_2017.pdf.txtelmo_amaral_etal_IOC_2017.pdf.txtExtracted texttext/plain68489https://www.arca.fiocruz.br/bitstream/icict/26681/3/elmo_amaral_etal_IOC_2017.pdf.txtb9dfcbf17875d932ee80fe68af29c506MD53icict/266812018-08-15 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dc.title.pt_BR.fl_str_mv Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B
title Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B
spellingShingle Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B
Velásquez, Angela Maria Arenas
Leishmania amazonensis
Trypanosoma cruzi
topoisomerase 1B
Leishmaniose
complexo ciclopaladado
Doença de Chagas
cyclopalladated complex
leishmaniasis
Chagas Disease
Leishmania amazonensis
Trypanosoma cruzi
Leishmania donovani
topoisomerase 1B
title_short Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B
title_full Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B
title_fullStr Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B
title_full_unstemmed Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B
title_sort Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B
author Velásquez, Angela Maria Arenas
author_facet Velásquez, Angela Maria Arenas
Ribeiro, Willian Campos
Venn, Vutey
Castelli, Silvia
Camargo, Mariana Santoro de
Assis, Renata Pires de
Souza, Rodrigo Alves de
Ribeiro, Aline Rimoldi
Passalacqua, Thaís Gaban
Rosa, João Aristeu da
Baviera, Amanda Martins
Mauro, Antonio Eduardo
Desideri, Alessandro
Amaral, Elmo Eduardo Almeida
Graminha, Marcia A. S.
author_role author
author2 Ribeiro, Willian Campos
Venn, Vutey
Castelli, Silvia
Camargo, Mariana Santoro de
Assis, Renata Pires de
Souza, Rodrigo Alves de
Ribeiro, Aline Rimoldi
Passalacqua, Thaís Gaban
Rosa, João Aristeu da
Baviera, Amanda Martins
Mauro, Antonio Eduardo
Desideri, Alessandro
Amaral, Elmo Eduardo Almeida
Graminha, Marcia A. S.
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Velásquez, Angela Maria Arenas
Ribeiro, Willian Campos
Venn, Vutey
Castelli, Silvia
Camargo, Mariana Santoro de
Assis, Renata Pires de
Souza, Rodrigo Alves de
Ribeiro, Aline Rimoldi
Passalacqua, Thaís Gaban
Rosa, João Aristeu da
Baviera, Amanda Martins
Mauro, Antonio Eduardo
Desideri, Alessandro
Amaral, Elmo Eduardo Almeida
Graminha, Marcia A. S.
dc.subject.other.pt_BR.fl_str_mv Leishmania amazonensis
Trypanosoma cruzi
topoisomerase 1B
Leishmaniose
complexo ciclopaladado
Doença de Chagas
topic Leishmania amazonensis
Trypanosoma cruzi
topoisomerase 1B
Leishmaniose
complexo ciclopaladado
Doença de Chagas
cyclopalladated complex
leishmaniasis
Chagas Disease
Leishmania amazonensis
Trypanosoma cruzi
Leishmania donovani
topoisomerase 1B
dc.subject.en.pt_BR.fl_str_mv cyclopalladated complex
leishmaniasis
Chagas Disease
Leishmania amazonensis
Trypanosoma cruzi
Leishmania donovani
topoisomerase 1B
description Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil / Universidade do Estado de São Paulo. Instituto de Química. Araraquara, SP, Brasil.
publishDate 2017
dc.date.issued.fl_str_mv 2017
dc.date.accessioned.fl_str_mv 2018-05-30T12:07:03Z
dc.date.available.fl_str_mv 2018-05-30T12:07:03Z
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 VELÀSQUEZ, Angela Maria Arenas; et al. Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B. Antimicrobial Agents and Chemotherapy, v.61, n.8, e00688-17, 15p, Aug. 2017.
dc.identifier.uri.fl_str_mv https://www.arca.fiocruz.br/handle/icict/26681
dc.identifier.issn.pt_BR.fl_str_mv 0066-4804
dc.identifier.doi.none.fl_str_mv 10.1128/AAC.00688-17
dc.identifier.eissn.none.fl_str_mv 1098-6596
identifier_str_mv VELÀSQUEZ, Angela Maria Arenas; et al. Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B. Antimicrobial Agents and Chemotherapy, v.61, n.8, e00688-17, 15p, Aug. 2017.
0066-4804
10.1128/AAC.00688-17
1098-6596
url https://www.arca.fiocruz.br/handle/icict/26681
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 American Society for Microbiology
publisher.none.fl_str_mv American Society for Microbiology
dc.source.none.fl_str_mv reponame:Repositório Institucional da FIOCRUZ (ARCA)
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instacron_str FIOCRUZ
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reponame_str Repositório Institucional da FIOCRUZ (ARCA)
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