Avaliação da atividade Leishmanicida de compostos organopaladados com ligantes nitrogenados e substituintes haletos e pseudohaletos

Abstract

Leishmaniasis is a disease caused by a protozoan from the genus Leishmania. It is considered a neglected disease with high endemicity in developing countries. The chemotherapy options are limited and the common problems are: long duration of therapy, high cost, parasite resistance, variable efficacy between strains or species, several drug side effects and toxicity. The need for new safe and effective therapeutic agents with less toxicity is urgent. The HIV/Leishmania co-infection has increased around of the world, changing the geographical distribution and the incidence of the disease. The study of transition metals activities has been conducted since the discovery of the antitumor activity of platinum (Pt) in 1965. The complexes of palladium (II) have been noted especially for its various biological activities as anti-tumor activity, anti-protozoal, anti-inflammatory action and leishmanicidal activity, and to be less toxic than the Pt. Due to necessity of new therapeutic agents, twelve new palladium (II) complexes obtained from two imine ligands were synthesized and characterized by elemental analyses, Infrared (IR) and 1H NMR spectroscopies. The in vitro evaluation of ligands and complexes has been tested on promastigotes and amastigotes form of Leishmania (Leishmania) amazonensis and its cytotoxicity determinate on murine macrophages, by MTT test. Most complexes exhibited a leishmanicidal activity which ranged from 5,72-53,01 µg/mL for IC50.The activity of ligands were improved after coordination with palladium and the replacement by some substituents had increased even more the leishmanicidal activity. The most active compounds were chloride (serie A) and thiocyanate complexes (both series). Besides the results indicated a potential leishmanicidal activity, the new compounds have lower cytotoxicity and higher selectivity index that Pentamidine, a drug reference. Therefore, these new compounds are promising agents in the treatment against leishmaniasis but further evaluation should be conducted to determine in vivo toxicity and mechanism of action.