In vitro evaluation and in vivo efficacy of nitroimidazole-sulfanyl ethyl derivatives against Leismania (V.) braziliensis and Leishmania (L.) mexicana

The aim of this study was the synthesis of several small molecules of the type nitroimidazole-sulfanyl, and the evaluation of the biological properties against the main species that cause cutaneus leishmaniasis in Venezuela. Final compounds (4-7) were generated through simple nucleophilic substitution of 1-(2- chloroethyl)-2-methyl-5-nitroimidazole 3 with 2-mercaptoethanol, 1-methyl-2-mercaptoethanol and 2-thiolacetic acid derivative. Compound 8 was synthesized via a coupling reaction between 7 and an amino acid. The inhibitory concentrations (IC₅₀) of (1-8) against Leismania (V.) braziliensis and (L.) mexicana in promastigotes and macrophages were determined by in vitro activity assays. For the in vivo evaluation of the more active compounds 7 and 8, the animals were infected with promastigotes of the two species and divided into four groups of ten (10) animals, and a control group. Two ways were used to the treatment intramuscular and intralesional. The parasitological diagnosis was determinate by PCR. Considering the defined parameters, compounds 7 and 8 showed in vitro and in vivo activity against L. (V.) braziliensis and L. (L.) mexicana. These compounds may represent an alternative treatment for this two species, which are the most important, from the epidemiological point of view, to produce cutaneous leishmaniasis in Venezuela.