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

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Abstract

β-Lactoglobulin (β-LG), the most important whey protein, has high capacity for binding many small hydrophobic molecules. The binding properties of β-LG in the presence of four different synthetic curcumin-based derivatives as potent inhibitors of intestinal α-glucosidase (α-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 β-LG was investigated using spectroscopic techniques. The spectroscopic analyses results propose acceptable binding affinities between the curcumin derivatives and β-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 β-LG based on the structural and thermodynamic analyses. Binding constant of complex formation (K) and thermodynamic parameters (ΔG°, ΔH° and ΔS°) 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 β-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 β-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.

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Abbreviations

β-LG:

β-Lactoglobulin

ANS:

1-Anilinonaphthalene-8-Sulfonic acid

MVD:

Molegro Virtual Docker

PDB:

Protein data bank

CGenFF:

CHARMM general force field

GROMACS:

Groningen machine for chemical simulation

PME:

Particle mesh ewald

RMSD:

Rout mean square deviation

RMSF:

Root mean square fluctuation

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Acknowledgements

The authors appreciatively acknowledge the financial support of Shiraz University Research Council, Iran National Science foundation (INSF).

Funding

This work was supported by INSF (Grant number 960084).

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Authors and Affiliations

  1. Protein Chemistry Laboratory (PCL), Department of Biology, College of Sciences, Shiraz University, Shiraz, Iran

    Afsoon Yousefi & Reza Yousefi

  2. Department of Pharmaceutical Biotechnology and Pharmaceutical Sciences Research Center, Faculty of Pharmacy, Shiraz University of Medical Sciences, Shiraz, Iran

    Sajjad Ahrari & Younes Ghasemi

  3. Department of Chemistry, College of Sciences, Shiraz University, Shiraz, Iran

    Farhad Panahi

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  1. Afsoon Yousefi
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Correspondence to Reza Yousefi.

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Yousefi, A., Ahrari, S., Panahi, F. et al. Binding analysis of the curcumin-based synthetic alpha-glucosidase inhibitors to beta-lactoglobulin as potential vehicle carrier for antidiabetic drugs. J IRAN CHEM SOC 19, 489–503 (2022). https://doi.org/10.1007/s13738-021-02323-8

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