Anais do Congresso Paranaense de Microbiologia
IV Congress of Microbiology in Paraná

Chagas disease (CD) is a neglected tropical disease that affects millions of people, particularly in Latin America where it is considered endemic. However, due to population mobility, the number of CD cases has increased in various regions of the world. This disease is caused by the protozoan Trypanosoma cruzi, whose transmission occurs through contact with a triatomine insect infected with the parasite. In Brazil, the treatment of CD is based on the use of the drug benzonidazole, however, it is an effective drug only in the acute phase of the disease and generates severe adverse effects, which decreases the rate of adherence to treatment. Therefore, new compounds for the treatment of CD are urgently needed. Thiohydantoins represent an important class of heterocyclic compounds that have several biological properties, including antimicrobial activity. Thus, the objective of this work was to evaluate the action of synthetic thiohydantoins against the parasite and animal cells in vitro. To carry out the study, a series of ten thiohydantoins was synthesized using cyclization reactions from L-amino acids. The substances were obtained in good yields (52-95%) and were properly characterized by spectroscopic techniques. Epimastigote cells of T. cruzi, strain Y, were grown in LIT medium, supplemented with 10% SFB, and kept in an incubator at 28°C for 72 h. Subsequently, the antiprotozoal effect of thiohydantoins was evaluated by incubating the substances (6.25-100 µg/mL) with the epimastigote forms of T. cruzi Y strain at 28 o C for 72 h. The toxicity of the compounds to mammalian cells was evaluated in LLC-MK2 cells using the MTT reduction assay. All compounds inhibited the growth of epimastigote forms, with IC 50 values (the lowest concentration capable of inhibiting cell proliferation by 50%) ranging from 12.77 to 152.84 µg/ml. The most active compounds PGC03, PGC24 and PGC26 exhibited IC 50 values of 20.49, 19.93 and 12.77 µg/ml, respectively. CC 50 values (the lowest concentration capable of reducing cell viability of 50% of cells) equal to 563.08, 427.5 and 493.51 µg/mL were determined for PGC03, PGC24 and PGC26, respectively, indicating that these compounds were more toxic to the parasite. Our results reveal an antiprotozoal effect of thiohydantoins on T. cruzi, indicating their potential for the development of new drugs for the control of Chagas disease.