Spectroscopic Methodology and Molecular Docking Studies on Changes in Binding Interaction of Felodipine with Bovine Serum Albumin Induced by Cocrystallization with β-Resorcylic Acid

Abstract

In the present study, a novel cocrystal of felodipine (FEL) and β-resorcylic acid (βRA) was developed. We specially focused on the change of binding pattern with bovine serum albumin (BSA) induced by cocrystallization of FEL with βRA. The solid characterizations and density functional theory (DFT) simulation verified that FEL-βRA cocrystal formed in equimolar ratio (1 : 1 M ratio) through C O … H-O hydrogen bond between C O group in FEL and O-H group in βRA. The binding interactions between FEL-βRA system and BSA were studied using fluorescence spectral and molecular docking methods. Two guest molecule systems, including a physical mixture of FEL and βRA and FEL-βRA cocrystal were performed binding to BSA in molecular docking. According to the K b and binding energy, the supramolecular form of FEL-βRA system was retained during binding to BSA. Molecular docking simulation suggested that FEL and its cocrystal inserted into the subdomain IIIA (site II′) of BSA. The interactions between FEL and BSA including hydrogen bonding with ASN390 residue and intermolecular hydrophobic interactions with LEU429 and LEU452 residues. However, the size of supramolecular FEL-βRA better matched that of active cavity of BSA; the cocrystal is closely bound to BSA through hydrogen bonding with ASN390 residue and intermolecular hydrophobic interactions with LEU429, VAL432, LEU452 and ILE387 residues. This change on binding affinity of FEL to BSA induced by cocrystallization with βRA provided theoretical basis to evaluate the transportation, distribution and metabolism of cocrystal drug.