Synthesis and Biological Evaluation of Chalcone Derivatives: α-Amylase and Trypsin Inhibition and Serum Protein Interaction Studies
Swati Sharma, komal DhingraIntroduction:
α,β-unsaturated ketones are a class of chalcones with beneficial pharmacological properties. Enhanced biological activity can be achieved by introducing halogens while maintaining, or even improving, their binding interactions with enzymes in the body. The present study outlines the targeted synthesis of chalcones as antidiabetic and anti-inflammatory agents by evaluating their inhibitory activity against amylase and trypsin. Moreover, serum protein protection assays for therapeutic safety were carried out for the synthesized chalcones. Additionally, to evaluate the antidiabetic and anti-inflammatory potential of chalcones, molecular docking was performed.
Methods:
The halo-substituted chalcones were prepared by the mechanical grinding method, thermal synthesis, microwave synthesis, and solvent-free neat-melt synthesis. From the aforementioned methods, 12 compounds were selected for melting point, FTIR, 1H-NMR, and 13C Nuclear Magnetic Resonance (NMR) spectra. In addition, this study performed mass spectrometry analysis. The enzymatic activity of the isolated compounds was screened for inhibition of α- amylase and trypsin; meanwhile, molecular docking with AutoDock Vina was performed.
Results:
All the selected chalcones showed moderate inhibition of α-amylase and trypsin. Compared with those of other compounds, the inhibitions for Compounds C25 and C26 were highest. However, docking studies suggested that C25 and C26 had considerable binding affinities for porcine α-amylase (-8.6 and -8.9 kcal/mol) and trypsin (-7.7 and -8.0 kcal/mol), and this was confirmed by π-π stacking, hydrophobic, and halogen interactions.
Discussion:
Enhanced activity of C25 and C26 is attributed to increased halogen substitution, which strengthens enzyme-ligand interactions. Experimental results showed good agreement with docking predictions, confirming the structure-activity relationship.
Conclusion:
Halo-substituted chalcones synthesized via green methods exhibit promising α- amylase and trypsin inhibition, with C25 and C26 identified as lead candidates for future drug development and discovery.