| Abstrakt: |
1,2,3-Triazole is one of the most flexible chemical scaffolds broadly used in various fields. Here, we report the antileishmanial activity of 1,2,3-triazole derivatives, the ultrastructural alterations induced by their treatment, and the nitric oxide (NO) modulation effect on their efficacy against Leishmania amazonensisin vitroinfection. After the screening of eleven compounds, compound 4exhibited better results against L. amazonensispromastigotes (IC50= 15.52 ± 3.782 μM) and intracellular amastigotes (IC50= 4.10 ± 1.136 μM), 50% cytotoxicity concentration at 84.01 ± 3.064 μM against BALB/c peritoneal macrophages, and 20.49-fold selectivity for the parasite over the cells. Compound 4induced ultrastructural mitochondrial alterations and lipid inclusions in L. amazonensispromastigotes, upregulated tumor necrosis factor α, interleukin (IL)-1β, IL-6, IL-12, and IL-10 messenger RNA expressions, and enhanced the NO production, verified by nitrite (p= 0.0095) and inducible nitric oxide synthase expression (p= 0.0049) quantification, which played an important role in its activity against intramacrophagic L. amazonensis. In silicoprediction in association with antileishmanial activity results showed compound 4as a hit compound with promising potential for further studies of new leishmaniasis treatment options. |
