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

Avwioroko, Oghenetega J. and Oyetunde, Temidayo T. and Atanu, Francis O. and Otuechere, Chiagoziem A and Anigboro, Akpovwehwee A. and Dairo, Oluropo F. and Ejoh, Akpoyovware S. and Ajibade, Sunday O. and Omorogie, Martins O. (2020) Exploring the binding interactions of structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase: Spectroscopic approach coupled with molecular docking. Biochemistry and Biophysics Reports, 24.

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Abstract

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 1H 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 F¨orster 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.

Item Type:	Article
Uncontrolled Keywords:	α-Amylase inhibition Ligand-protein binding Spectroscopy Hyperglycemia Anti-diabetic agents
Subjects:	Q Science > QH Natural history Q Science > QH Natural history > QH301 Biology
Divisions:	Faculty of Medicine, Health and Life Sciences > School of Biological Sciences
Depositing User:	nwokealisi
Date Deposited:	19 May 2023 10:00
Last Modified:	19 May 2023 10:00
URI:	http://eprints.covenantuniversity.edu.ng/id/eprint/16900

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