Copyright © 2003 BioChem Press A Multivariate Study on the Inhibition of the Xanthine Oxidase by Phenylpyrazole Compounds

In this work, a set of phenylpyrazole compounds was studied in order to determine the molecular properties responsible for their previously tested ability to inhibit the xanthine oxidase (XO) enzyme. Several electronic, steric and lipophylic properties were calculated by quantum chemical methods from the geometries optimized by the DFT/B3LYP method. The chemometric methods PCA, HCA and SDA were employed to find the subset of variables that could correctly classify the compounds according to their inhibitory activity. The PCA, HCA and SDA results showed that four variables can be considered as relevant for the XO inhibitory activity: µ (dipole moment), QR2 (total charge of the substituent R2), D3 (torsion angle formed by the atoms C6-C1-C2-R2) and MR (molar refractivity). From the PCA, HCA and SDA results in this work, a classification model was built with the aim to be used in the search for phenylpyrazole compounds that present XO inhibitory activity