CONICET | Buscador de Institutos y Recursos Humanos

Chagas disease, caused by Trypanosoma cruzi, is a major public health problem in Latin America. According to the World Health Organization, around 20 million people are infected and another 40 million are at risk of acquiring the disease. Currently, chemotherapy of the disease is based in two old drugs, Benznidazole and Nifurtimox, which are not effective and highly toxic especially in the chronic stage of the disease. For these reasons, new drugs to replace the outdated and ineffective therapy are required. To this end, we have produced a series of hybrids of Cinchona alkaloids and bile acids, expecting to combine their anti-parasitic activity and the known properties as drug transporters, respectively. These chimeric compounds were synthesized by a Barton-Zard decarboxylation reaction and have shown promising activity against T. brucei, L. mexicana mexicana and P. falciparum. Moreover, we have recently demonstrated that these compounds have antiparasitic activity against different Trypanosoma cruzi DTUs. In this work, new hybrids, with modifications in the bile acid fraction, have been tested for cytotoxicity assayed on HeLa cells. Half maximal inhibitory concentration (IC50) against these cells were estimated ranging between [1.0 ? 3.0 ug/ml]. Besides, we tested the compounds against two T. cruzi strains (DTUs II and VI) tripomastigotes forms and the IC50 were estimated between [0.15 ? 0.6 ug/ml]. Compounds activity against amastigote forms was less effective than the observed against tripomastigote forms. Selectivity of the hybrids were calculated as IC50HeLa/IC50tripomastigote form and some compound showed values of 10 or higher. This study opens the door to new possibilities in the screening of alternative drugs used traditionally in the Chagas disease?s treatment.