<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

Optimization of Antitrypanosomatid Agents: Identification of Nonmutagenic Drug Candidates with in Vivo Activity

Chagas disease, caused by <i>Trypanosoma cruzi</i> parasite, was described thousands of years ago. Currently, it affects millions of people, mostly in Latin America, and there are not suitable drugs for treating it. As an attempt to find appropriate drugs to deal with this problem, we report here on the design, synthesis, and characterization of 82 new compounds. Trypanosomicidal behavior in vitro showed more than 20 outstanding derivatives with anti-<i>Trypanosoma cruzi</i> activity. Furthermore, we studied the nonspecific toxicity against mammalian cells determining their selectivity and also performed mutagenicity studies. Proof of concept, in vivo studies, was conducted with two of the most promising derivatives (<b>77</b> and <b>80</b>). They were identified as candidates because they have (i) very simple and cost-effective syntheses; (ii) activity against different stages and strains of the parasite showing excellent in vivo behavior during the acute phase of Chagas disease; and (iii) neither nonspecific toxicity nor mutagenic activity