Synthesis and Characterization of Benzalacetone Derivatives Evaluated by In Vitro Antidiabetic Studies and In Silico Molecular Docking

This study reports the synthesis and characterization of a series of benzalacetone, dibenzalacetone, and their derivatives, aimed at exploring their potential as pharmacological leads. The compounds were prepared via crossed aldol condensation and structurally confirmed using 1H-NMR and FTIR spectroscopy along with melting point analysis. Their biological activities were evaluated, focusing on serum protein protecting activity, trypsin, and α-amylase inhibition studies. Molecular docking studies were employed to complement the experimental findings and elucidate the binding interactions with bovine serum albumin (BSA, PDB ID: 4f5s), trypsin (PDB ID: 1AVW), and α-amylase (PDB ID: 1DHK). Among the synthesized derivatives, compound 4c exhibited the highest inhibitory activity against trypsin (76%) and BSA (72%), while compound 4d demonstrated the strongest inhibition of α-amylase (73%). Docking analysis confirmed that protein–ligand binding was mainly driven by hydrogen bonding, van der Waals, and electrostatic interactions, supporting the observed biological activities.