Síntese e estudo de derivados de benzotiazóis contra o parasita Leishmania infantum.

Abstract

Leishmaniasis is a pandemic disease caused by vector parasites of the genus Leishmania. These phagocyte parasites use blood-sucking sandflies, as hosts and transmitters of the disease. There are several types of leishmaniasis, being the most dangerous the visceral form, which is caused by the parasite Leishmania infantum, very common in countries with a tropical climate and with regions of social vulnerability, such as Brazil. For the treatment of the disease, there are drugs that are effective, but that contain many side effects, so it is necessary to study and research for new drugs in order to improve the treatment. So, studies with benzothiazole groups, which are already known in the pharmaceutical industry for their considerable biological activity, were initiated. With studies, using benzothiazoles against the parasite Trypanossoma cruzi, studies against Leishamnia infatum were also initiated, since both are part of the family Trypanosomatidae of the phylum of protozoa that are characterized by a single axoneme and an organelle known as kinetoplast, a mitochondria rich in deoxyribonucleic acid. Therefore, having similar characteristics in the cellular structure and in the form of contamination, it was identified the possibility of studying compounds tested for Trypanossoma cruzi, to be tested also for Leishamnia infatum. With this, an initial structure was tested and three types of modifications were made to it. Through different amines, with amidation reactions in the presence of EDC and HOBt, to verify possible improvements or reduction in the values of IC50, CC50 and IS, compared to the reference compound (IC50: 5,5 5,5 uM; CC50: 203 uM; IS: 36,3), as these are important parameters in the evaluation of a compound for subsequent in vivo testing and for potential drugs. Compounds 8, 9 and 10 were successfully synthesized and purified, obtaining a yield of 42%, 47% and 55% and with biological results (IS: 4.3; 19.8; 5.5 respectively). In this way, we obtained the results that all synthesized molecules had lower biological activity effects than the reference compound, but which served as a basis for us to understand a little more about this class that is so important in pharmacology studies and how these compounds behave with the structural modifications.