Estudo in vitro da atividade anti-leishmania de compostos sintéticos derivados espiro-acridínicos sobre leishmania amazonensis.

Abstract

Leishmaniasis are anthropozoonoses caused by protozoa of the genus Leishmania and transmitted by female sandflies during blood meal. This set of diseases causes great mortality and morbidity in the human being and over the years it has been neglected due to the few resources applied in diagnosis, treatment and control. The disease is endemic in more than 98 countries, including Brazil, which has the highest number of cases among countries in the Americas. Currently, more than 50 species are classified, more than 20 are pathogenic to humans, which cause a variety of clinical manifestations, such as visceral leishmaniasis and cutaneous leishmaniasis, the latter being the most common. The only treatment options are medications, such as pentavalent antimonials, amphotericin B, pentamidines, miltefosine and pentoxifylline in addition to other therapies that are used as adjuvants. The medications have several limitations, such as side effects and high toxicity. These factors are decisive for the search for new therapeutic agents in the fight against Leishmaniasis. Therefore, we evaluated the anti-Leishmania activity of spiro-acridine derivatives and the reference drug against promastigote forms of L. amazonensis and its cytotoxicity against human erythrocytes. The activity of the compounds on the promastigote forms and human erythrocytes were evaluated by the MTT colorimetric test (3- (4,5-dimethylthiazol-zyl) -2,5-diphenyltetrazolium bromide). The results showed that the spiro-acridine derivatives (AMTAC 10 and AMTAC 13) and the reference drug showed activity against L. amazonensis promastigotes, with an IC50 of 2.91 ± 1.664 μg/mL, 6.37 ± 2.035 μg/mL and 0.82 ± 0.03882 μg/mL, respectively. The reference drug showed greater cytotoxicity against human erythrocytes compared to spiro-acridine derivatives. The selectivity index revealed that the spiro-acridine derivatives have greater selectivity for parasites than blood cells when compared to the reference drug. Thus, we observed that the spiro-acridine derivatives have an effective anti-leishmania activity against promastigote forms and do not present toxicity to human blood cells. New tests must be carried out to discover the mechanism of action to be used in the treatment of leishmaniasis.