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
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2017 |
| 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/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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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. |
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2017 |
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2017 |
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2018-05-30T12:07:03Z |
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2018-05-30T12:07:03Z |
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info:eu-repo/semantics/article |
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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. |
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https://www.arca.fiocruz.br/handle/icict/26681 |
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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 |
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American Society for Microbiology |
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American Society for Microbiology |
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