Avaliação in silico de propriedades antichagásicas e farmacocinéticas de compostos candidatos a novos fármacos

Abstract

Chagas disease originates from the protozoa Trypanosoma cruzi. It has been causing great damages to population and it is now spreading throughout non-endemic regions such as United States, Europe and Japan. The treatment is carried through the use of two medications (nifurtimox and benznidazole) that have shown serious side effects and low efficiency. The main goal of this research is to contribute to the search of new bioactive chemicals for contribute to the treatment of Chagas disease. For this purpose compound database denominated 'Base Tcruzi' has been built and experiments 'in silico' were carried out in order to evaluate the potential of the molecules being studied as candidates to drugs. Two virtual experiments were done: determination of the pharmacokinetic features, determination of the chemical similarity and the docking to the validated target to execute the trypanocidal activity, the GAPDH. The most efficient compounds showed an potential to optimizations in the future, with properties drug like and were more active than the benznidazole standard. With the results from the 'in silico' screening, it was possible to come to the conclusion that in 'Base Tcruzi' there are 56 molecules with optimized molecular properties and have outstanding potential as candidates to antichagasic agents.