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Title: In Vitro and in Vivo Activity of an Organic Tellurium Compound on Leishmania (Leishmania) chagasi
Authors: Pimentel, Isabella Aparecida Salerno [UNIFESP]
Paladi, Carolina de Siqueira [UNIFESP]
Katz, Simone [UNIFESP]
Judice, Wagner Alves de Souza [UNIFESP]
Cunha, Rodrigo Luiz Oliveira Rodrigues [UNIFESP]
Barbieri, Clara Lucia [UNIFESP]
Universidade Federal de São Paulo (UNIFESP)
Univ Mogi das Cruzes
Universidade Federal do ABC (UFABC)
Issue Date: 7-Nov-2012
Publisher: Public Library Science
Citation: Plos One. San Francisco: Public Library Science, v. 7, n. 11, 7 p., 2012.
Abstract: Tellurium compounds have shown several biological properties and recently the leishmanicidal effect of one organotellurane was demonstrated. These findings led us to test the effect of the organotellurium compound RF07 on Leishmania (Leishmania) chagasi, the agent of visceral leishmaniasis in Latin America. in vitro assays were performed in L. (L.) chagasi-infected bone marrow derived macrophages treated with different concentrations of RF07. in in vivo experiments Golden hamsters were infected with L. (L.) chagasi and injected intraperitoneally with RF07 whereas control animals received either Glucantime or PBS. the effect of RF07 on cathepsin B activity of L. (L.) chagasi amastigotes was assayed spectrofluorometrically using fluorogenic substrates. the main findings were: 1) RF07 showed significant leishmanicidal activity against intracellular parasites at submicromolar concentrations (IC50 of 529.7+/-26.5 nM), and the drug displayed 10-fold less toxicity to macrophages (CC50 of 5,426+/-272.8 nM); 2) kinetics assays showed an increasing leishmanicidal action of RF07 at longer periods of treatment; 3) one month after intraperitoneal injection of RF07 L. (L.) chagasi-infected hamsters showed a reduction of 99.6% of parasite burden when compared to controls that received PBS; 4) RF07 inhibited the cathepsin B activity of L. (L.) chagasi amastigotes. the present results demonstrated that the tellurium compound RF07 is able to destroy L. (L.) chagasi in vitro and in vivo at concentrations that are non toxic to the host. We believe these findings support further study of the potential of RF07 as a possible alternative for the chemotherapy of visceral leishmaniasis.
ISSN: 1932-6203
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