Spectral characterization of the binding and conformational changes of serum albumins upon interaction with an anticancer drug, anastrozole

The present study employed different optical spectroscopic techniques viz., fluorescence, FTIR, circular dichroism (CD) and UV–vis absorption spectroscopy to investigate the mechanism of interaction of an anticancer drug, anastrozole (AZ) with transport proteins viz., bovine serum albumin (BSA) and human serum albumin (HSA). The drug, AZ quenched the intrinsic fluorescence of protein and the analysis of results revealed the presence of dynamic quenching mechanism. The binding characteristics of drug–protein were computed. The thermodynamic parameters, enthalpy change (ΔH°) and entropy change (ΔS°) were calculated to be +92.99 kJ/mol and +159.18 J/mol/K for AZ–BSA and, +99.43 kJ/mol and +159.19 J/mol/K for AZ–HSA, respectively. These results indicated that the hydrophobic forces stabilized the interaction between the drug and protein. CD, FTIR, absorption, synchronous and 3D fluorescence results indicated that the binding of AZ to protein induced structural perturbation in both serum albumins. The distance, r between the drug and protein was calculated based on the theory of Förster's resonance energy transfer and found to be 5.9 and 6.24 nm, respectively for AZ–BSA and AZ–HSA.

The present study employs multi-spectroscopic techniques to characterize the mechanism of binding of an anticancer drug, anastrozole (AZ) with serum albumins viz., bovine serum albumin (BSA) and human serum albumin (HSA). The fluorescence data shows the presence of dynamic quenching mechanism. Hydrophobic forces were observed to stabilize the interaction between the drug and protein. The binding distance, r between the drug and protein was calculated based on the theory of Förster's resonance energy transfer and found to be 5.9 and 6.24 nm, respectively for AZ–BSA and AZ–HSA. CD, FTIR, absorption, synchronous and 3D fluorescence results indicated that the binding of AZ to protein induced structural perturbation in both serum albumins.Figure optionsDownload as PowerPoint slideHighlights
► Interaction of anastrozole with serum protein was studied by spectroscopic methods.
► Fluorescence quenching data suggested the presence of dynamic quenching mechanism.
► Hydrophobic forces played a major role in the binding of the drug to protein.
► CD, FTIR and 3D fluorescence data revealed conformational changes in the protein.