Antileishmanial Evaluation of Bark Methanolic Extract of Acacia nilotica: In Vitro and In Silico Studies

[Image: see text] Acacia nilotica (A. nilotica) is an important medicinal plant, found in Africa, the Middle East, and the Indian subcontinent. Every part of the plant possesses a wide array of biologically active and therapeutically important compounds. We reported the antileishmanial activity of A. nilotica bark methanolic extract through in vitro antileishmanial assays and dissected the mechanism of its action through in silico studies. Bark methanolic extract exhibited antipromastigote and antiamastigote potential in a time and dose-dependent manner with IC(50) values of 19.6 ± 0.9037 and 77.52 ± 5.167 μg/mL, respectively. It showed cytotoxicity on THP-1-derived human macrophages at very high dose with a CC(50) value of 432.7 ± 7.71 μg/mL. The major constituents identified by gas chromatography–mass spectrometry (GC–MS) analysis, 13-docosenoic acid, lupeol, 9,12-octadecadienoic acid, and 6-octadecanoic acid, showed effective binding with the potential drug targets of Leishmania donovani (L. donovani) including sterol 24-c-methyltransferase, trypanothione reductase, pteridine reductase, and adenine phosphoribosyltransferase, suggesting the possible mechanism of its antileishmanial action. Pharmacokinetic studies on major phytoconstituents analyzed by GC–MS supported their use as safe antileishmanial drug candidates. This study proved the antileishmanial potential of bark methanolic extract A. nilotica and its mechanism of action through the inhibition of potential drug targets of L. donovani.