3D-QSAR studies on lipid peroxidation inhibitory activity of chromone derivatives

Lipid peroxidation has been implicated in disease states such as atherosclerosis, asthma, neurodegenerative disorders, Parkinson’s disease, cancer, etc. In this study, the anti-lipid peroxidation activity for a series of chromone compounds, evaluated in vitro by ferric thiocyanate and thiobarbituric acid assays, were subjected to three-dimensional quantitative structure-activity relationship studies using comparative molecular field analysis and comparative molecular similarity indices analysis. From ferric thiocyanate assay, the best comparative molecular field analysis and comparative molecular similarity indices analysis models gave cross-validated r 2 ( q 2 ) = 0.563 and 0.593 and non cross-validated r 2 = 0.974 and 0.929, respectively. The best comparative molecular field analysis and comparative molecular similarity indices analysis models derived from thiobarbituric acid assay gave q 2 = 0.558 and 0.612, and non cross-validated r 2 = 0.959 and 0.919, respectively. The generated hydrogen donor contour maps support the previously reported structure-activity relationship that the presence of a catechol moiety in ring A is essential for high potency.