6 research outputs found
Exploring the binding interactions of structurally diverse dichalcogenoimidodiphosphinate ligands with α-amylase: Spectroscopic approach coupled with molecular docking
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
a-Amylase inhibition, anti-glycation property and characterization of the binding interaction of citric acid with a-amylase using multiple spectroscopic, kinetics and molecular docking approaches
The quest to suppress complications associated with diabetes mellitus is ever increasing, while food additives
and preservatives are currently being considered to play additional roles besides their uses in food
enhancement and preservation. In the present study, the protective prowess of a common food preservative
(citric acid, CA) against advanced glycation end-products (AGEs) formation and its binding interaction
mechanism with a-amylase (AMY), an enzyme linked with hyperglycemia management, were
examined. Enzyme inhibition kinetics, intrinsic fluorescence, synchronous and 3D fluorescence spectroscopies,
ultraviolet–visible (UV–Vis) absorption spectroscopy, Fourier transform-infrared (FT-IR) spectroscopy,
thermodynamics, and molecular docking analyses were employed. Results obtained showed
that citric acid decreased a-amylase activity via mixed inhibition (IC50 = 5.01 ± 0.87 mM,
Kic = 2.42 mM, Kiu = 160.34 mM) and suppressed AGEs formation (IC50 = 0.795 ± 0.001 mM). The intrinsic
fluorescence of free a-amylase was quenched via static mechanism with high bimolecular quenching
constant (Kq) and binding constant (Ka) values. Analysis of thermodynamic properties revealed that
AMY-CA complex was spontaneously formed (DG DH), with involvement
of electrostatic forces. UV–Vis, FT-IR and 3D fluorescence spectroscopies affirmed alterations in aamylase
native conformation due to CA binding interaction. CA interacted with His-101, Asp-197, His-
299, and Glu-233 within AMY active site. Our findings indicated that CA could impair formation of
AGEs and interact with a-amylase to slow down starch hydrolysis; vital properties in management of
type 2 diabetes complications
Cardioprotective Effects of Curcumin-Nisin Based Poly Lactic Acid Nanoparticle on Myocardial Infarction in Guinea Pigs
Abstract Myocardial infarction (MI) is the most prevalent cause of cardiovascular death. A possible way of preventing MI maybe by dietary supplements. The present study was thus designed to ascertain the cardio-protective effect of a formulated curcumin and nisin based poly lactic acid nanoparticle (CurNisNp) on isoproterenol (ISO) induced MI in guinea pigs. Animals were pretreated for 7 days as follows; Groups A and B animals were given 0.5 mL/kg of normal saline, group C metoprolol (2 mg/kg), groups D and E CurNisNp 10 and 21 mg/kg respectively (n = 5). MI was induced on the 7th day in groups B-E animals. On the 9th day electrocardiogram (ECG) was recorded, blood samples and tissue biopsies were collected for analyses. Toxicity studies on CurNisNp were carried out. MI induction caused atrial fibrillation which was prevented by pretreatment of metoprolol or CurNisNp. MI induction was also associated with increased expressions of cardiac troponin I (CTnI) and kidney injury molecule-1 (KIM-1) which were significantly reduced in guinea pig’s pretreated with metoprolol or CurNisNp (P < 0.05). The LC50 of CurNisNp was 3258.2 μg/mL. This study demonstrated that the formulated curcumin-nisin based nanoparticle confers a significant level of cardio-protection in the guinea pig and is nontoxic