Design, Synthesis, Molecular Docking, In Silico ADMET, and Biological Evaluation of 3-Benzylidene-2-phenylchroman-4-one Derivatives as Pancreatic Lipase Inhibitors

In the present study, a series of 3-benzylidene-2-phenylchroman-4-one analogs were synthesized via condensation of flavanone with substituted aromatic aldehydes. The synthesized derivatives were screened in vitro to understand their inhibitory potential against pancreatic lipase. Derivative B8 exhibited potent inhibitory activity towards pancreatic lipase (IC50 = 0.015 ± 0.00076 µM) close to that the standard drug orlistat (0.014 ± 0.00073 µM). The enzyme kinetics study reveals that B8 exhibited reversible mixed-type inhibition with an inhibitory constant value of 0.003825 µM. Molecular docking of synthesized compounds agreed with in vitro results, as the dock scores showed a significant correlation with their inhibitory activity. The in silico toxicity profile reflects that the synthesized analogues are safer and suitable for in vivo analysis. The present study identified 3-benzylidene-2-phenylchroman-4-one derivatives with promising potential as pancreatic lipase inhibitors, and further lead optimization could result in potency enhancement.