Binding of the Inclusion Complex of Atorvastatin-β-cyclodextrin to Bovine Serum Albumin

Document Type: Research Paper

Authors

1 Department of Chemistry, Muthayammal College of Arts and Science, Rasipuram 637408, Tamil Nadu, India

2 Department of Chemistry & Department of Nanoscience, Karunya Institute of Technology and Sciences (Deemed-to-be University), Coimbatore 641114, Tamil Nadu, India

3 Department of Chemistry, Sri Shakthi Institute of Engineering and Technology, Coimbatore 641062, Tamil Nadu, India

Abstract

The objective of the paper is to determine the effect of β-cyclodextrin complexation on the interaction of the popular drug, Atorvastatin to bovine serum albumin. Fluorescence and 2D Rotating-frame Overhauser effect spectroscopic techniques are used to determine the stoichiometry, the binding contant, and the mode of binding of Atorvastatin to β-cyclodextrin. The role of the Atorvastatin–β-cyclodextrin complexation in modulating the binding strength of the drug to the model carrier protein bovine serum albumin is studied using absorption and fluorescence spectral measurements and molecular docking. Atorvastatin shows a fluorescence enhancement on comlplex formation with β-cyclodextrin. The results of the binding of the drug to bovine serum albumin in free– and β-cyclodextrin–bound forms. The magnitude of quenching of the fluorescence of bovine serum albumin due to drug binding, an d the Fӧrster energy transfer efficiency between the protein and the drug are decreased in the presence of β-cyclodextrin. The binding constant value of the drug–protein binding in the absence and presence of β-cyclodextrin are 5.36 × 104 M-1 to 2.32 × 104 M-1 respectively. Atorvastatin forms a 1:2 inclusion complex with cyclodextrin. The isopropyl substituent in the pyrrole ring of Atorvastatin binds to β-cyclodextrin. Cyclodextrin modulated the binding of drug to the serum albumin, i.e., the cyclodextrin complex of Atorvastatin binds to bovine serum albumin with diminished binding strength. Nevertheless, the exposed part of the drug is found to be sufficient for interaction with the same binding pocket as the free drug binds to.

Keywords


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