Quantitative correlation between theoretical molecular descriptors and drug‐HSA binding affinities for various cox‐2 inhibitors

Abstract

In this study, quantitative structure-protein binding relationships have been derived to predict the binding affinities of cox-2 inhibitor drugs to HSA from the structure of drug molecules. Drug-HSA binding affinities were determined using fluorescence spectroscopic technique. For the calculation of theoretical molecular descriptors and statistical treatment of data dragon, codessa and spss software were used. In the quantitative structure-protein binding model, one-parameter correlations were statistically not very sound. Quadratic equations gave better fit of the data in some cases. Two-parameter correlations could explain 94-98% of the variance in the data. Steric, geometric and topological descriptors outweighed all other parameters in the developed quantitative structure-protein binding relationships. There was some contribution from electrostatic descriptors as well, but the role of hydrophobic binding was completely ruled out in the protein binding of coxibs. The quantitative correlations derived in this paper are useful in predicting the protein binding of coxibs and may help in the design of cox-2 inhibitors with appropriate HSA binding properties.