Binding analysis of the curcumin-based synthetic alpha-glucosidase inhibitors to beta-lactoglobulin as potential vehicle carrier for antidiabetic drugs

beta-Lactoglobulin (beta-LG), the most important whey protein, has high capacity for binding many small hydrophobic molecules. The binding properties of beta-LG in the presence of four different synthetic curcumin-based derivatives as potent inhibitors of intestinal alpha-glucosidase (alpha-Gls) were investigated. To study the binding properties both UV-vis and florescence spectroscopy were used accompanied by molecular modeling and simulation. The formed complex between curcumin and beta-LG was investigated using spectroscopic techniques. The spectroscopic analyses results propose acceptable binding affinities between the curcumin derivatives and beta-LG. Also, it was proved that the hydrophobic interactions play a noteworthy role in the protein-ligand binding. All of the curcumin inhibitors showed high affinity to beta-LG based on the structural and thermodynamic analyses. Binding constant of complex formation (K) and thermodynamic parameters (Delta G degrees, Delta H degrees and Delta S degrees) of complex formation were calculated. The results suggested that the process was endothermic and entropy driven. Moreover, our results indicated that protein-ligand binding was spontaneous signifying the presence of static quenching between the two molecules. Our finding suggests the major role of hydrophobic effect in the interaction of the synthetic compounds and beta-LG. Moreover, molecular docking analyses exposed that curcumin-based ligands bind with high affinity to the protein in a hydrophobic pocket which located on the protein surface. The stability of ligand-protein interaction was further confirmed by molecular dynamics simulation analysis. This study suggests beta-LG as a good carrier for these potentially curcumin-based antidiabetic compounds to deliver safely through the stomach to small intestine which is the crucial site of their activity.