Molecular docking studies reveal the phytocompound of Acacia pennata responsible for the potential inhibition of α- glucosidase

Abstract

The aqueous extract of the shoot tips of Acacia pennata showed a high enzyme inhibitory activity against α-glucosidase. However, the enzyme inhibiting phytocompound is not known. Identification of the antidiabetic phytocompound will be beneficial in designing drugs with higher efficacy to treat diabetes mellitus. We attempted to identify the compound using molecular docking simulation studies (MDSS). Among the 29 phytocompounds present in A. pennata, MDSS revealed that 23 phytocompounds outperformed the co-crystal inhibitor (CCI) of α -glucosidase (PDB ID: 5NN5) in terms of binding affinity. Among the 23 phytocompounds, (2R)-4’,7-dihydroxyflavan-(4aà8)-(2R,3S)-3,5,7-trihdyroxyflavan- 3”-O-α-L-rhamnopyranoside (compound 25) has the highest binding affinity (-9.2 kcal/mol). Analysis of the protein-ligand interactions revealed that compound 25 formed 5 conventional hydrogen bonds (ASP 282, TRP 481, ARG 600, ASP 616, HIS 674), 3 hydrophobic interactions (TRP 376, TRP 481, LEU 650), 3 electrostatic interactions (MET 519, ASP 616 (n=2)), and 1 carbon-hydrogen bond (ASP 518). The binding pose analysis further revealed that the docking protocol applied in the study was able to re-dock the CCI and dock compound 25 exactly at the active binding site where the CCI was originally positioned. Our in-silico study showed that compound 25 is the phytocompound of A. pennata that is responsible for potentially inhibiting the α-glucosidase enzyme. The structure of compound 25 may be modified to design more potent inhibitors of α-glucosidase.