In vitro antileishmanial activity and molecular docking studies of lupeol and monostearin, isolated from Parkia biglobosa

Abstract

Parkia biglobosa (Leguminosae) is used traditionally for managing leishmaniasis. However, there are no reports of the antileishmanial constituents from the plant. This study is aimed at isolating antileishmanial compounds, from the stem bark of P. biglobosa, and assessing their mechanism of action using molecular docking studies. Bioassay-guided fractionation led to the isolation of two known compounds, lupeol and monostearin. Their structures were elucidated using their mass spectra. Using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymathoxyphenyl)-2-(4-sulfophenyl)-2H-tretrazolium (MTS) assay, the evaluated antileishmanial effects of lupeol (1) and monostearin (2) showed IC50 values of 164.42 and 151.99 µg/mL respectively. The antileishmanial effects of the crude extract, non-polar, mid-polar and polar fractions were determined to be 64.43, 126.25, 725.65 and 167.52 µg/mL respectively. Molecular docking studies of the two isolates within the active sites of two validated targets in the Leishmania parasite: trypanothione reductase (TR) and pteridine reductase 1 (PTR1), showed that both compounds established important interactions with key amino acid residues in both proteins. Lupeol exhibited binding affinities of -7.1 kcal/mol and -10.2 kcal/mol for TR and PTR1, respectively, better than monostearin in both cases. Our findings back the claim that P. biglobosa stem bark possesses antileishmanial effects. Furthermore, the isolates lupeol and monostearin may be partly responsible for the observed activities.