Síntese e caracterização de uma classe de sulfonilpiperazinas com potencial atividade contra Leishmania Infantum, agente causador da Leishmaniose.

Abstract

Leishmaniasis is a parasitic disease caused by the protozoan Leishmania infantum; it is considered by the World Health Organization to be a neglected tropical disease. Currently, there is no cure for this disease, and the main form of treatment is the drugs Glucantime and Amphotericin B. These drugs have a certain efficiency in treatment, however, they have high toxicity and severe side effects. In this context, it is necessary to develop new, more efficient, less toxic and low-cost drugs for the treatment of this disease. In this work, three compounds from a class of sulfonylpiperazines were synthesized and characterized, based on work previously carried out by our research group in which a series of compounds with potential activity against T. cruzi (the causative agent of Chagas' disease) and L. infantum were studied, based on the planning and chemical modifications to the fragments of a prototype compound (initial hit) in order to improve their biological activities. After analyzing the work, three new modifications were planned, namely to the benzenesulfononyl fragment, where the carbonyl of the amino-aryl fragment and the meta ratio between oxygen and nitrogen of piperazine were maintained. The three derivatives were synthesized in 4 steps and characterized by 1Hand 13CNMR. After synthesizing and characterizing the compounds, biological tests were carried out against L. infantum. The results showed that the compounds had a decrease in activity against L. infantum compared to the compounds previously obtained by the group, since the IC50 of the most active compound is 0.59 μM and the best biological activity obtained in this work was 4.96 μM for derivative 4c. This work contributes to the understanding of the relationship between chemical structure and biological activity of compounds of the sulfonylpiperazine class and to the development of new drug candidates against Leishmaniasis.