Topological Descriptors in Modeling Tumor Necrosis Factor alpha Inhibitory Activity of Xanthines, Pteridinediones and Related Compounds
BioChem Press, Hemant Kumar Jain, Ram Kishore Agrawal, H. S. Gour Vishwavidyalaya · 2007
Motivation. Inhibition of tumor necrosis factor alpha (TNF–D ) is an important strategy for the treatment of various inflammatory, infectious, immunological, or malignant diseases such as Crohn’s disease, rheumatoid arthritis and psoriasis. Therefore, the TNF–D inhibitory activity of xanthines, pteridinediones and related compounds has been analyzed with different topostructural and topochemical indices. Method. The quantitative structure–activity relationships (QSAR) study was performed using derivatives of xanthines, pteridinediones and related compounds with Dragon 3.0 structural descriptors. The relationship between inhibitory activity and various descriptors is established by step–wise multiple regression analysis using Systat 10.2 and Valstat. Results. The analyses have generated significant and predictive QSAR models. The values of statistical indices for QSAR with simple topological descriptors is R = 0.91, F = 19.92, SEE = 24 and R 2 CV = 0.68; for QSAR with more complex topological descriptors is R = 0.90, F = 25.74, SEE = 0.23 and R 2 CV = 0.67 and for QSAR with mixed classes of descriptors is R = 0.93, F = 25.93, SEE = 0.21 and R 2 CV = 0.73. Conclusions. These models suggest that Lopping centric index, fourth order bond information content of neighbourhood symmetry, polarizability and electronegativity weighted Geary graph spatial autocorrelation coefficient of the first lag, atomic masses weighted Moran graph spatial autocorrelation coefficient of the third lag, and average connectivity indexF 1 have a direct correlation with the biological activity. The average valence connectivity indexF 3 , electronegativity weighted Geary graph spatial autocorrelation coefficient of the seventh lag, electronegativity weighted Moran graph spatial autocorrelation coefficient of the fifth lag and number of substituted aromatic sp 2 carbon have an inverse correlation with the biological activity.