Determination of the in vivo activity of leaves extract of Zanthoxylum Chiloperone var. Angustifolium (Tembetary hú) orally and intralesionally administered to BALB/c mice experimentally infected with Leishmania

Natural products are becoming increasingly important as an unlimited source for obtaining chemical substances with possible pharmacological potential. Current existing drugs for the treatment of cutaneous leishmaniosis produce major side effects; therefore the search for new drugs is justified. The stem bark of Zanthoxylum chiloperone var. Angustifolium Engl. (Rutaceae) is traditionally used in Paraguay for its antiparasitic properties. The leaf extract was evaluated for the first time to determine its leishmanicidal activity in BALB/c mice infected with amastigote forms of Leishmania amazonensis (PH8). The mice were treated orally with the extract at three concentrations (100, 50 and 10 mg/mL), intralesional (50 mg/mL), and subcutaneously using glucantime as a control (100 mg/mL). The percentage of decrease in parasite load was measured and with intralesional 50 mg/kg a reduction of 72% occurred, with the reference drug (Glucantime) a reduction of 62% was obtained with the same oral dose a reduction of 50%, while with an oral dose of 10 mg/mL the percentage of reduction was 55%. When the oral dose was increased to 100 mg/mL, the reduction percentage of the parasitic load was only 16%. These results indicated that the leaf extract of Z. chiloperone var. angustifolium Engl. at low oral concentrations (50 and 10 mg/mL) had very good activity against L. amazonensis, and it was even more efficacious intralesionally at 50 mg/mL but at the oral dose of 100 mg/kg has very reduced antiparasitic activity. This study showed the efficacy of the extract leaves of Z. chiloperone in reducing the parasite load in an in vivo test, so its use as a potential leishmanicidal could be suggested to develop and evaluate new drugs for the oral treatment of leishmaniosis disease with fewer side effects and lower cost

In vitro and in vivo antitrypanosomatid activity of 5-nitroindazoles

Previously, we have identified a series of 5-nitroindazoles with good antiprotozoal activities, against Trypanosoma cruzi epimastigotes and Trichomonas vaginalis. Most of them have shown very low unspecific toxicity on macrophage cell lines. In the present work, we assayed these compounds on T. cruzi bloodstream trypomastigotes and Leishmania promastigotes (Leishmania amazonensis, Leishmania braziliensis and Leishmania infantum). Derivatives 1, 2, 7 and 8 displayed remarkable trypanocidal activity (>80% lysis) equivalent to gentian violet. Derivatives 2 and 10, as Pentamidine, caused the complete lysis of promastigotes of Leishmania. An oxidative stress-mediated mechanism of action was confirmed for derivatives 1, 10 and 12 on T. cruzi epimastigotes. Supported by the in vitro activities, derivatives 1 and 2 were submitted to in vivo assays using an acute model of Chagas' disease and a short-term treatment. None of the animals treated with derivatives 1 and 2 died, unlike the untreated control and Benznidazole groups

Preclinical Studies and Drug Combination of Low-Cost Molecules for Chagas Disease

Chagas disease is caused by the protozoan Trypanosoma cruzi (T. cruzi). It remains the major parasitic disease in Latin America and is spreading worldwide, affecting over 10 million people. Hundreds of new compounds with trypanosomicidal action have been identified from different sources such as synthetic or natural molecules, but they have been deficient in several stages of drug development (toxicology, scaling-up, and pharmacokinetics). Previously, we described a series of compounds with simple structures, low cost, and environmentally friendly production with potent trypanosomicidal activity in vitro and in vivo. These molecules are from three different families: thiazolidenehydrazines, diarylideneketones, and steroids. From this collection, we explored their capacity to inhibit the triosephosphate isomerase and cruzipain of T. cruzi. Then, the mechanism of action was explored using NMR metabolomics and computational molecular dynamics. Moreover, the mechanism of death was studied by flow cytometry. Consequently, five compounds, 314, 793, 1018, 1019, and 1260, were pre-clinically studied and their pharmacologic profiles indicated low unspecific toxicity. Interestingly, synergetic effects of diarylideneketones 793 plus 1018 and 793 plus 1019 were evidenced in vitro and in vivo. In vivo, the combination of compounds 793 plus 1018 induced a reduction of more than 90% of the peak of parasitemia in the acute murine model of Chagas disease

<i>Helietta apiculata:</i> a tropical weapon against Chagas disease

<p>The present study pretends to evaluate the <i>in vivo</i> efficacy of the crude chloroform bark extract of <i>Helietta apiculata</i>, then the activity will be compared with the reference drug, benznidazole, in acute <i>Trypanosoma cruzi</i> infected mice when administered by oral route. The chloroformic extract of <i>Helieta apiculata</i> was administered by oral route at 5, 10 and 50 mg/kg daily for two weeks. This study has shown a moderate efficacy of the <i>H. apiculata</i> bark extract in reducing <i>T. cruzi</i> parasitaemia in 42 to 54% after a monitoring of 60 days post-infection and when compared with control groups. Concerning mice mortality, only two only two mice died, one from the control group and the other one from the group threated with 10 mg of the chlorofom extract of <i>H. apiculata</i>, suggesting the potential of <i>H. apiculta</i> extracts as a safe and inexpensive treatment of Chagas disease.</p