Avaliação da atividade leishmanicida de derivados tiossemicarbazônicos

Abstract

Leishmaniasis is a group of neglected diseases that affects mainly emerging countries. It is caused by protozoa of the genus Leishmania and transmitted through the blood meal performed by the female sand fly. It has two evolutionary forms: promastigotes, which have a flagellum and are found in the digestive tract of the vector, and amastigotes, or no flagellated, found in vertebrate tissues. The disease has two main clinical forms: cutaneous leishmaniasis and visceral leishmaniasis, the latter being the most serious, as it compromises viscera and can lead the patient to death. According to the World Health Organization, leishmaniasis is endemic in 102 countries or territories. Despite the great complexity of the disease, the therapeutic arsenal is still quite limited, based on the use of pentavalent antimonies as drugs of first choice and liposomal amphotericin B and pentamidine as second choice drugs. However, these drugs have problems such as high cytotoxicity, significant adverse effects and parasitic resistance. In view of this problematic reality, emerges the need of searching for new candidates for prototypes of leishmanicidal drugs, which have a low toxicity and a high leishmanicidal effect. The present study evaluated the cytotoxicity of 19 thiosemicarbazonic derivatives (T1 to T19) and pentamidine against macrophages of the J774.A1 strain, in the appropriate 100, 30, 10 and 3 μM, where it was possible to trace the Lethal Concentration (CL50) and determine the maximum cytotoxic effect of the derivatives. At the maximum concentration tested, that is, at 100 μM, T13, T14, T15 and T16 showed no damage to the host cell and at the concentration of 10 μM, derivatives T5, T8 and T13 did not show cytotoxic effect. Based on these results, a pharmacological screening was carried out in order to assess the leishmanicidal potential at a concentration of 10 μM against the amastigote form of Leishmania amazonensis, where the compounds T8, T10, T11, T12 and T18 showed a maximum effect above 60%, 71.2 ± 2.5%; 61.3 ± 8.9%; 68.5 ± 6.4%; 64.9 ± 1.3% and 61.3 ± 8.9%, respectively. As T8 was the derivative that showed a high leishmanicidal effect while not causing damage to macrophages, it can be considered as promising for further studies to determine the 50% inhibitory concentration (IC50) and its evaluation as a candidate for drug prototype leishmanicides.