Study on the interaction of anti-inflammatory drugs with human serum albumin using molecular docking, quantitative structure-activity relationship, and fluorescence spectroscopy

The interaction of 14 anti-inflammatory drugs with human serum albumin (HSA) was investigated using fluorescence quenching, molecular docking studies, and quantitative structure-activity relationship (QSAR) methodology. Binding of anti-inflammatory drugs to HSA plays a fundamental role in their transport, distribution, delivery, and elimination. Binding constants of these drugs to HSA, obtained using the fluorescence quenching method, were within the range 0.01 x 10(4) M-1 (acetaminophen) to 1881.05 x 10(4) M-1 (meloxicam). Binding sites and binding constants of these anti-inflammatory drugs were estimated using molecular docking. Inspection of the obtained values for docking score, logK(b) and K-b, showed that the drugs in this data set have a relatively strong binding constant for HSA. QSAR modelling was applied for binding constants obtained from fluorescence quenching and theoretical molecular descriptors. This modelling led to a linear two-parameter model with a correlation coefficient of 0.95 and adequate robustness. The descriptor results showed the importance of a bonding network and electronegativity as the discriminative structural factors in binding affinity for the HSA molecule.