Luminescence and in-silico studies of binding interactions of arylpiperazinyl-butylbenzoxazolone based synthetic compounds with bovine serum albumin

Abstract

5-HT7, a G-protein coupled receptor of CNS is important in regulating various functions of brain. This study demonstrates the binding interactions of 5-HT specific six synthesized arylpiperazinyl-butylbenzoxazolone (APBBO) derivatives (L1, L2, L3, L4, L5 and L6) with bovine serum albumin (BSA) involving photophysical and CD measurements. Besides that the binding interactions of synthesized compounds in the binding pockets of BSA were visualized using molecular docking analysis. The effect of binding of these synthesized compounds on enzymatic activity of BSA was ascertained by a bioassay based on esterase-like activity. Under the influence of APBBO derivatives, the UV–vis absorbance and fluorescence measurements indicated alteration in polarity around the microenvironment of protein. The quantum yield of fluorescence emission of BSA was quenched, and the fluorescence quenching was essentially static quenching. Binding constant values were observed in the range of 104–106 M−1 which indicated the dominance of non-covalent binding interactions. This was further supported from the thermodynamic parameters (ΔH, ΔS) and molecular docking studies, which illustrated hydrophobic interactions and H-bonding as main player in this binding interaction. The CD experimental studies confirmed that the α-helix and β-sheet structure of serum protein altered when APBBO ligands bind to them. In the case of L4, a maximum increase in α-helix content (22.6 %) and a maximum decrease in β-sheet content (18.1 %) were recorded. Furthermore, for esterase-like catalytic activity, L1, L3, and L4 reduced the catalytic activity and L2, L5 and L6 enhanced the catalytic activity.