Design, synthesis, evaluation of biological activity against Trypanosoma cruzi and QSAR studies of a series of oxadiazolines compounds

Abstract

Chagas' disease is endemic for 21 countries affecting about 18 million people, also, being responsible for high rates of morbidity and mortality. As malaria, schistosomiasis and filariasis, Chagas' disease is considered a neglected tropical disease, because does not offer sufficient financial returns for pharmaceutical industries to engage in research and development areas. In Brazil, during the last 30 years, benznidazole is the only currently drug used for its therapy. However, it is not effective during the chronic stage of the disease and produce serious side effects, resulting, many times, in the treatment interruption. The development of a new drug is a hard and expensive process, so, the improvement of structures with well known biological activity, associated with computational tools used in medicinal chemistry, as molecular modeling and studies of Quantitative Structure-Activity Relationships, QSAR, is a reasonable alternative to reduce the investment, increasing the chances of success. With this approach, a series of 5-nitroheterocyclic derivatives has been synthesized and identified with potential action against Trypanosoma cruzi, etiological agent of Chagas' disease. The variability of biological activity of a series of analogs can be related to the compound chemical structure, analyzed by QSAR studies, which consider physical and chemical properties of substitutes groups. According to these statements, this project aims to design and evaluate the anti-chagasic activity of 5-nitro-heterocyclics oxadiazolines derivatives compounds, to perform 2D-QSAR and 3D-QSAR studies, selecting potential candidates to become new anti-chagasic agents. (AU)