Quinoxalines against Leishmania amazonensis: SAR study, proposition of a new derivative, QSAR prediction, synthesis, and biological evaluation

Abstract

Neglected tropical diseases, such as leishmaniasis, lead to serious limitations to the affected societies. In this work, a structure-activity relationship (SAR) study was developed with a series of quinoxaline derivatives, active against the promastigote forms of Leishmania amazonensis. As a result, a new quinoxaline derivative was designed and synthesized. In addition, a quantitative structure-activity relationship (QSAR) model was obtained [pIC₅₀ = - 1.51 - 0.96 (E_HOMO) + 0.02 (PSA); N = 17, R² = 0.980, R²_Adj = 0.977, s = 0.103, and LOO-cv-R² (Q²) = 0.971]. The activity of the new synthesized compound was estimated (pIC₅₀ = 5.88) and compared with the experimental result (pIC₅₀ = 5.70), which allowed to evaluate the good predictive capacity of the model.