Avaliação biológica de pirimidinas sintéticas contra Leishmania amazonensis e L. chagasi

Abstract

Leishmaniasis, a neglected tropical disease (NTD) caused by protozoa of the genus Leishmania spp., is transmitted by infected sand flies and is endemic in tropical and subtropical regions, especially in socioeconomically vulnerable regions. Currently available treatments have severe adverse effects, making it difficult for patients to adhere to pharmacotherapy. This study investigated the leishmanicidal activity of 14 new synthetic pyrimidines through in vitro assays with phagocytic cells and promastigotes of L. amazonensis and L. chagasi. The compounds were first evaluated for toxicity in J774. A1 lineage macrophages, 8 of which, with lower cytotoxicity, were subsequently tested against Leishmania promastigotes using amphotericin B as a positive control. The data were processed in the Prisma® software to obtain statistical parameters, such as significance level and inhibitory concentration values for 50% (IC50). The results indicate that the compounds IJS01 (IC50 (µM): 7.09 ± 4.20), IJS04 (IC50 (µM): 15.21 ± 2.43) and IJS07 (IC50 (µM): 22.85 ± 0 .88) in L. chagasi promastigotes and the compounds IJS02 (IC50 (µM): 6.978 ± 1.70) and IJS07 (IC50 (µM): 1.642 ± 0.98) in L. amazonensis may be promising for the development of new drugs against leishmaniasis as they present a considerable inhibitory effect at a low concentration in relation to the other compounds investigated.