Relevant studies have demonstrated that α-glucosidase represents a crucial target for diabetes treatment, and andrographolide (AO) exhibits notable inhibitory activity against this enzyme. In this research, the interaction mechanism between AO and α-glucosidase was investigated using UV-Vis, fluorescence analysis, FT-IR, circular dichroism (CD), and molecular docking techniques. AO induced static quenching of the fluorescent groups in α-glucosidase through a spontaneous reaction process (ΔG0 < 0), primarily driven by hydrogen bonds and van der Waals forces at a single binding site. The interaction between AO and α-glucosidase resulted in a reduction of the α-helix content while increasing the β-turn and random coil components within the secondary structure of α-glucosidase. A detailed analysis of molecular docking results revealed that AO interacted with Tyr158 and Tyr316 residues in α-glucosidase, leading to fluorescence quenching of the enzyme and enhancing the hydrophobicity surrounding these tyrosine residues. Furthermore, AO formed hydrogen bonds with Glu277, Arg315, Asn415, and Arg442 while generating van der Waals interactions along with hydrophobic forces involving Phe159 and other amino acid residues. Through these intermolecular interactions, AO bound to the active center's binding cavity in α-glucosidase, resulting in conformational changes that ultimately affect enzymatic activity.
Keywords: andrographolide; interaction; molecular docking; spectroscopy; α‐glucosidase.
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