Abstract

Liza T. Billones, and Junie B. Billones

DOI : http://dx.doi.org/10.13005/ojc/330509

Gout and oxidative stress have been strongly associated with hyperuricemia, a metabolic defect marked by high levels of uric acid (UA) in the serum. Hyperuricemia has been managed by the use of drugs that inhibit xanthine oxidase. The recent account on synthesis of 4-aryl/heteroaryl-4H-fused pyrans as XO inhibitors provided excellent opportunity to uncover the crucial properties of these compounds that confer XO inhibitory action. In here, multiple linear regression analysis of DRAGON-type descriptors showed that the Randic Shape Index (PW3), and a size descriptor P_VSA_v_3 account for the 75% of the variability of IC₅₀ values. Correlation studies with familiar QSAR descriptors indicate that the observed activity is primarily influenced by the molecular ovality and volume, and partly by charge distribution. The Comparative Molecular Field Analysis (CoMFA) models provide further insights on the steric and electronic features of this class of XO inhibitors.

Xanthine oxidase inhibitors (XOI); hyperuricemia; gout; fused pyrans; CoMFA; Randic Shape Index

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