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

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 [pIC(50) = - 1.51 - 0.96 (E-HOMO) + 0.02 (PSA); N = 17, R-2 = 0.980, R-Adj(2) = 0.977, s = 0.103, and LOO-cv-R-2 (Q(2)) = 0.971]. The activity of the new synthesized compound was estimated (pIC(50) = 5.88) and compared with the experimental result (pIC(50) = 5.70), which allowed to evaluate the good predictive capacity of the model.

Automated summary

Neglected tropical diseases, such as leishmaniasis, have significant impacts on affected societies. This study focused on the relationship between quinoxaline derivatives and the activity against Leishmania amazonensis. A new derivative was designed and synthesized, and a quantitative structure-activity relationship model was established, showing good predictive capacity.