Exploring the Binding Interactions of Structurally Diverse dichalcogenoimidodiphosphinate Ligands with α-amylase: Spectroscopic Approach Coupled with Molecular Docking
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Date
2020
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ELSEVIER Biochemistry and Biophysics Reports
Abstract
Postprandial hyperglycemia has orchestrated untimely death among diabetic patients over the
decades and regulation of α-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 α-amylase to ascertain the affinity of the ligands for α amylase using spectroscopic and molecular docking methods. The ligands were characterized using 1 H
and 31P NMR spectroscopy and CHN analysis. Diselenoimidodiphosphinate ligand (DY300),
dithioimidodiphosphinate ligand (DY301), and thioselenoimidodiphosphinate ligand (DY302) quenched
the intrinsic fluorescence intensity of α-amylase via a static quenching mechanism with bimolecular
quenching constant (Kq) values in the order of x1011 M-1s -1, indicating formation of enzyme-ligand
complexes. A binding stoichiometry of n≈1 was observed for α-amylase, with high binding constants
(Ka). α-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 (ΔG<0) between the ligands and α-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 α-amylase via some key catalytic site amino acid residues
(Asp197, Glu233 and Asp300). DY301 perhaps showed highest α-amylase inhibition (IC50, 268.11 ± 0.74
μM) 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 α-amylase inhibitors from
dichalcogenoimidodiphosphinate ligands for management of postprandial hyperglycemia
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Keywords
α-Amylase inhibition, Ligand-protein binding, Spectroscopy, Hyperglycemia, Anti-diabetic agents