Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/26681
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
Authors: 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.
Affilliation: Universidade 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.
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.).
Keywords: cyclopalladated complex
leishmaniasis
Chagas Disease
Leishmania amazonensis
Trypanosoma cruzi
Leishmania donovani
topoisomerase 1B
keywords: Leishmania amazonensis
Trypanosoma cruzi
topoisomerase 1B
Leishmaniose
complexo ciclopaladado
Doença de Chagas
Issue Date: 2017
Publisher: American Society for Microbiology
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.
DOI: 10.1128/AAC.00688-17
ISSN: 0066-4804
Copyright: open access
Appears in Collections:IOC - Artigos de Periódicos

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