Quinoxalines against Leishmania amazonensis: SAR study, proposition of a new derivative, QSAR prediction, synthesis, and biological evaluation
Anna Carolina Silva De Jesus Passaes, Juliana A. Dantas, Fernanda Landim Lopes, Diego Pereira Sangi, Magaly Girão Albuquerque, Celso Vataru Nakamura, Julliane Yoneda
Abstract
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 [pIC 50 = − 1.51 − 0.96 (E HOMO ) + 0.02 (PSA); N = 17, R 2 = 0.980, R 2 Adj = 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.