`Synthesis, Characterization, Hirshfeld Surface Analysis, Crystal Structure and Molecular Modeling Studies of 1-(4-(Methoxy(phenyl)methyl)-2-methylphenoxy)butan-2-one Derivative as a Novel alpha-Glucosidase Inhibitor

The crystal compound was synthesized and characterized using conventional analytical techniques. The compound C19H21O3 crystallizes in a monoclinic crystal system with the space group P21/c. The crystal structure is stabilized by C-H center dot center dot center dot O interactions. The structure is further reinforced by pi-pi interactions. During in vitro inhibition of ff-glucosidase, the crystal compound exhibited a significant inhibition of the enzyme (IC50: 10.30 +/- 0.25 mu g/mL) in comparison with the control, acarbose (IC50: 12.00 +/- 0.10 mu g/mL). Molecular docking studies were carried out for the crystal compound with the alpha-glucosidase protein model, which demonstrated that the crystal molecule has a good binding affinity (-10.8 kcal/mol) compared with that of acarbose (-8.2 kcal/mol). The molecular dynamics simulations and binding free energy calculations depicted the stability of the crystal molecule throughout the simulation period (100 ns). Further, a Hirshfeld analysis was carried out in order to understand the packing pattern and intermolecular interactions. The energy difference between the frontier molecular orbitals (FMO) was 4.95 eV.