Efeito de Diaril Dissulfetos sobre Trypanosoma cruzi

Abstract

Trypanosoma cruzi is a flagellated protozoan, considered the etiologic agent of Chagas disease. In Brazil, it is estimated that more than three million people suffer from this disease that despite investments in basic sanitation works and preventive actions for its control is still a serious health problem, affecting the most vulnerable people, especially those who live in rural areas and have poor housing conditions. The drugs currently used are not very effective in the chronic phase of the disease and have a series of side effects, in addition to mutagenic and carcinogenic activities. Some classes of organic compounds represent potential alternatives for the development of new drugs. This is the case of the diaryl disulfide class, whose compounds have interesting properties explored in several areas of synthetic and pharmaceutical chemistry and in the production of polymers. Therefore, this work aimed to evaluate five synthetic compounds of this class regarding the activity on T. cruzi epimastigotes. The methodology used involved biological tests to evaluate the metabolic viability and the growth of the parasites, in addition to the cytotoxicity test on Vero cells. Based on the results, it was observed that all compounds have biological activity on epimastigote forms of T. cruzi. Compounds A and D were the most active in in vitro treatment for 72h, with IC50 values of 3.5µM and 3.7µM, respectively. However, after 24 hours of parasite treatment, the most active compounds were D and E, with LC50 values of 0.7 µM and 0.9 µM, respectively. Regarding the evaluation of cytotoxicity on Vero cells, compounds A, C and E showed the highest CC50 values (34.1µM; 32.0µM and 30.5µM, respectively), while compound D was shown to be the most cytotoxic among the five tested. In the recovery curve, all compounds were able to inhibit the growth of the parasites within 96 hours after the drug was withdrawn. It was also observed that the target of action in the parasite probably depends on the position of the ligand in relation to the disulfide bond in the structure of the compounds. Such results indicate the action of diaryl disulfide compounds on mechanisms that influence the proliferation of T. cruzi, revealing promising data for future research.