Identification of α-glucosidase inhibitors from leaf extract using liquid chromatography-mass spectrometry-based metabolomics and protein-ligand interaction with molecular docking.

The present study used and techniques, as well as the metabolomics approach to characterise α-glucosidase inhibitors from different fractions of is a medicinal plant belonging to the Acanthaceae family, and is traditionally used to treat diabetes in Malaysia. Hexane, hexane: ethyl acetate (1:1, v/v), ethyl acetate, ethyl acetate: methanol (1:1, v/v), and methanol fractions were obtained via partitioning of the 80% methanolic crude extract. The α-glucosidase inhibitory activity was analyzed using all the fractions collected, followed by profiling of the metabolites using liquid chromatography combined with mass spectrometry. The partial least square (PLS) statistical model was developed using the SIMCA P14.0 software and the following four inhibitors were obtained: 4,6,8-Megastigmatrien-3-one; N-Isobutyl-2-nonen-6,8-diynamide; 1',2'-bis(acetyloxy)-3',4'-didehydro-2'-hydro-β, ψ-carotene; and 22-acetate-3-hydroxy-21-(6-methyl-2,4-octadienoate)-olean-12-en-28-oic acid. The study performed via molecular docking with the crystal structure of yeast isomaltase (PDB code: 3A4A) involved a hydrogen bond and some hydrophobic interactions between the inhibitors and protein. The residues that interacted include ASN259, HID295, LYS156, ARG335, and GLY209 with a hydrogen bond, while TRP15, TYR158, VAL232, HIE280, ALA292, PRO312, LEU313, VAL313, PHE314, ARG315, TYR316, VAL319, and TRP343 with other forms of bonding.