Leishmanicidal Activity of Quinoline Derivatives: Synthesis, Evaluation and Computational Studies

Abstract

Newer 3, 6, and 8-aminoquinoline substituted compoundsi.e. (10a-f, 11a-f and 12a-f) were synthesized and evaluated for their in-vitro antileishmanial activity against promastigote form of Leishmania donovani. Among the tested analogues, seven compounds (10a, 10f, 11f, 12a, 12c, 12d and 12f) exhibited significant antileishmanial activity in comparison to standard drug sitamaquine. Docking study was also performed to understand the interaction of newly synthesized compounds with binding sites. Aminoquinolinessubstituted with phthalimide(10f, 2f and 3f) exhibited better binding affinity (-8.5, -8.2 and -8.4)in respect to standarddrug (-6.9). In silico ADME prediction studies depicted that the newly synthesized compounds obeyed Lipinski's rule of five, exhibited better absorption and toxicity profile as compared to the standard drug.