Author | Velásquez, Angela Maria Arenas | |
Author | Ribeiro, Willian Campos | |
Author | Venn, Vutey | |
Author | Castelli, Silvia | |
Author | Camargo, Mariana Santoro de | |
Author | Assis, Renata Pires de | |
Author | Souza, Rodrigo Alves de | |
Author | Ribeiro, Aline Rimoldi | |
Author | Passalacqua, Thaís Gaban | |
Author | Rosa, João Aristeu da | |
Author | Baviera, Amanda Martins | |
Author | Mauro, Antonio Eduardo | |
Author | Desideri, Alessandro | |
Author | Amaral, Elmo Eduardo Almeida | |
Author | Graminha, Marcia A. S. | |
Access date | 2018-05-30T12:07:03Z | |
Available date | 2018-05-30T12:07:03Z | |
Document date | 2017 | |
Citation | 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. | pt_BR |
ISSN | 0066-4804 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/26681 | |
Language | eng | pt_BR |
Publisher | American Society for Microbiology | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | Leishmania amazonensis | pt_BR |
Subject in Portuguese | Trypanosoma cruzi | pt_BR |
Subject in Portuguese | topoisomerase 1B | pt_BR |
Subject in Portuguese | Leishmaniose | pt_BR |
Subject in Portuguese | complexo ciclopaladado | pt_BR |
Subject in Portuguese | Doença de Chagas | pt_BR |
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 | pt_BR |
Type | Article | pt_BR |
DOI | 10.1128/AAC.00688-17 | |
Abstract | 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.). | pt_BR |
Affilliation | Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil / Universidade do Estado de São Paulo. Instituto de Química. Araraquara, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil. | pt_BR |
Affilliation | University of Rome. TorVergata, Rome, Italy. | pt_BR |
Affilliation | University of Rome. TorVergata, Rome, Italy. | pt_BR |
Affilliation | University of Rome. TorVergata, Rome, Italy. | pt_BR |
Affilliation | Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil. | pt_BR |
Affilliation | Universidade do Estado de São Paulo. Instituto de Química. Araraquara, SP, Brasil. | pt_BR |
Affilliation | Universidade Estadual de Campinas. Instituto de Biologia. Campinas, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil / Universidade Estadual de São Paulo. Instituto de Químca. Araraquara, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil. | pt_BR |
Affilliation | Universidade do Estado de São Paulo. Instituto de Química. Araraquara, SP, Brasil. | pt_BR |
Affilliation | University of Rome. TorVergata, Rome, Italy. | pt_BR |
Affilliation | .Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Rio de Janeiro, RJ, Brasil. | pt_BR |
Affilliation | Universidade de São Paulo. Escola de Ciências Farmacêuticas. Araraquara, SP, Brasil. | pt_BR |
Subject | cyclopalladated complex | pt_BR |
Subject | leishmaniasis | pt_BR |
Subject | Chagas Disease | pt_BR |
Subject | Leishmania amazonensis | pt_BR |
Subject | Trypanosoma cruzi | pt_BR |
Subject | Leishmania donovani | pt_BR |
Subject | topoisomerase 1B | pt_BR |
e-ISSN | 1098-6596 | |