Exploring the binding interactions of structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase: Spectroscopic approach coupled with molecular docking

Y Postprandial hyperglycemia has orchestrated untimely death among diabetic patients over the decades and regulation of alpha-amylase activity is now becoming a promising management option for type 2 diabetes. The present study investigated the binding interactions of three structurally diverse dichalcogenoimidodiphosphinate ligands with alpha-amylase to ascertain the affinity of the ligands for alpha-amylase using spectroscopic and molecular docking methods. The ligands were characterized using 1H and 31P NMR spectroscopy and CHN analysis. Diselenoimidodiphosphinate ligand (DY300), dithioimidodiphosphinate ligand (DY301), and thioselenoimidodiphosphinate ligand (DY302) quenched the intrinsic fluorescence intensity of alpha-amylase via a static quenching mechanism with bimolecular quenching constant (Kq) values in the order of x10(11) M(-1)s(-1), indicating formation of enzyme-ligand complexes. A binding stoichiometry of n approximate to 1 was observed for alpha-amylase, with high binding constants (Ka). alpha-Amylase inhibition was as follow: Acarbose > DY301>DY300>DY302. Values of thermodynamic parameters obtained at temperatures investigated (298, 304 and 310 K) revealed spontaneous complex formation (Delta G<0) between the ligands and alpha-amylase; the main driving forces were hydrophobic interactions (with DY300, DY301, except DY302). UV-visible spectroscopy and Forster resonance energy transfer (FRET) affirmed change in enzyme conformation and binding occurrence. Molecular docking revealed ligands interaction with alpha-amylase via some key catalytic site amino acid residues (Asp197, Glu233 and Asp300). DY301 perhaps showed highest alpha-amylase inhibition (IC50, 268.11 +/- 0.74 mu M) due to its moderately high affinity and composition of two sulphide bonds unlike the others. This study might provide theoretical basis for development of novel alpha-amylase inhibitors from dichalcogenoimidodiphosphinate ligands for management of postprandial hyperglycemia.