Anti-Trypanosoma activity of hybrid of bile acids and natural alkaloids

N FELDMAN; J L ESCALONA; A LEVERRIER; J PALERMO; M EDREIRA; A D MUSIKANT;

Mar del Plata

Simposio; XXXI Reunion Anual Sociedad Argentina de Protozoologia; 2019

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. The current treatment for the Chagas disease continues to be one of the main reasons why this disease is not yet eradicated. First choice drugs, Benznidazole and Nifurtimox, have a bad performance, including no pediatric formulation and high toxicity, especially in the chronical stage of the disease. For these reasons, it is necessary to find alternative compounds to treat the disease. 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 synthetized 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.