Infecção assintomática por Leishmania em humanos e atividades biológicas de alcaloides β-carbolinas

Abstract

Leishmaniasis are neglected, non-contagious tropical parasitic diseases caused by species of protozoa belonging to the genus Leishmania that affect thousands of people around the world. The development of clinical forms can lead to the appearance of skin lesions, even disfiguring ones, involvement of lymphoid organs or even cases of asymptomatic infection. Considering the problems in treating the disease due to drug toxicity and parasitic resistance, it is necessary that new molecules be studied and evaluated for their anti-Leishmania effects, in an attempt to develop new therapeutic alternatives. In this context, the objective of the work was to develop a systematic review on asymptomatic infection in humans, and to investigate the chemical characteristics and in silico toxicity, as well as the hemolytic potential, anti-Leishmania and antioxidant activity of eleven synthetic alkaloids from the β-carboline class. The systematic review study after applying inclusion and exclusion criteria included 82 articles. It was demonstrated that the largest number of studies with asymptomatic cases was carried out in Brazil (n= 27) and India (n= 15); With the articles analyzed, it was possible to identify the species of Leishmania reported in the studies, as well as techniques used for diagnosis, population analyzed, age range and history of pre-existing diseases. For the development of the second study, the β-carboline compounds were obtained through chemical synthesis reported in a previous study, and through their chemical structures, with the help of servers, it was possible to analyze the chemical characteristics and in silico toxicity of these molecules. The anti-Leishmania activity against promastigote forms of Leishmania amazonensis was determined by the colorimetric method using MTT. Cytotoxicity was evaluated using human erythrocytes and antioxidant activity was measured using DPPH and ABTS assays. The 11 derivatives analyzed demonstrated good lipophilicity and solubility parameters and were not mutagenic or cytotoxic. The IC50 for the promastigote forms varied between compounds (IC50 = 5.15 to 41.19 μM), with the PNO2-Anis derivative (8) demonstrating better anti-Leishmania potential. None of the compounds showed hemolytic potential. Regarding antioxidant activity, the Cl-Oxa derivative (11) stands out (IC50 = 0.0481 μM) in the DPPH assay. As for the ABTS assay, all compounds demonstrated better antioxidant potential than the BHT control. Despite the results demonstrated, future studies of these prototypes are necessary in an attempt to use them for the treatment of leishmaniasis.