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Internet Electronic Journal of Molecular Design - IEJMD, ISSN 1538-6414, CODEN IEJMAT
| ABSTRACT - Internet Electron. J. Mol. Des. July 2005, Volume 4, Number 7, 515-526 |
A Multivariate Study on the Inhibition of the Xanthine Oxidase by Phenylpyrazole Compounds
Saulo L. da Silva, Sérgio Marangoni, Karen C. Weber, Paula Homem-de-Mello, Káthia M. Honório, and Albérico B.F. da Silva
Internet Electron. J. Mol. Des. 2005, 4, 515-526
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Abstract:
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 reliable classification model was built, as the
cross-validation error is equal to 0%. This indicates that
this model can be used in the search for new
phenylpyrazole compounds that present XO inhibitory activity.
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