Acacia 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 and has been used in the traditional system of medicine. We reported the antileishmanial activity of Acacia nilotica (A. nilotica) bark methanolic extract through in vitro assays and dissected the mechanism of its action through in silico studies. Bark methanolic extract exhibited anti-promastigote and anti-amastigote potency with IC50 value of 19.6 ± 0.9037 μg/ml and 77.52 ± 5.167 μg/ml respectively in time and dose-dependent manner.
It showed very low cytotoxicity having a CC50 value of 432.7 ± 7.71 μg/ml on the human-macrophage cell line, THP-1. The major constituents identified by GC-MS analysis are 13-docosenoic acid (34.06%), lupeol (20.15 %), 9,12-octadecadienoic acid (9.92 %), and 6-octadecanoic acid (8.43 %) bind effectively with the potential drug-targets of Leishmania donovani (L. donovani) including sterol 24-c-methyltransferase (SMT), trypanothione reductase (TR), pteridine reductase (PTR1) and adenine phosphoribosyltransferase (APRT); suggest the possible mechanism of its antileishmanial action. The highest affinity with all these targets was shown by lupeol. The pharmacokinetic studies, predicted bioactivity scores, and acute toxicity studies of major extract constituents support 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.