Planejamento, síntese e avaliação da atividade anti-Leishmania de derivados de benzofenona

Abstract

Leishmaniasis is a vector-borne disease that is widespread in several areas, mainly in tropical, subtropical and developing countries, where the presence of insect vectors is larger. Mammalian hosts contract the disease when they are bitten by the infected female of the transmitting insect, creating a biological cycle of proliferation of the Leishmania parasite. Its high mortality rate and the use of drugs that cause undesired harmful effects have aroused great interest among researchers for the development of drugs that are easier to administer and with fewer adverse effects such as pain at the application site, cardio, gastrotoxicity and others. This work aims to plan and demonstrate new drug candidates with structures derived from benzophenones, which are easy to administer and highly active against the Leishmania parasite. Initially, the planning was carried out using a classification method that was developed based on the data of antileishmanial activity that has been already published. It was conducted a detailed and thorough search in the literature for benzophenones derivatives with an assessment of antiLeishmania activity. We also considered data for xanthones due to their structural similarity with benzophenones and based on the compiled data, some statistical analyzes were performed to help choose the best chemical descriptors and substituents responsible for the reported activity. Therefore, from the result of the method, new substances were proposed, and the most promising ones were synthesized, then, the method developed to predict the activity of some derivatives pre-available in the laboratory was used. These structures were evaluated in vitro against the promastigote and amastigote forms of Leishmania amazonensis and Leishmania chagasi respectively, which showed very promising CI50 values below 30 μM. By the results of the classification method we consider it to be appropriate for predicting the activity of new derivatives since it has achieved a hit rate of 86%.