Free Radical Scavenging Activity Evaluation of Hydrazones by Quantitative Structure Activity Relationship

The 2, 2-diphenyl-1-picrylhydrazyl (DPPH) free radical scavenging properties of selected hydrazone antioxidants was investigated by the application of Quantitative Structure Activity Relationship (QSAR). Density functional theory (DFT) was employed in the optimization of the molecular structures. Internal and external validation as well as y-randomization tests were conducted in order to confirm the statistical reliability and acceptability of the developed models. The leverage approach was employed in the assessment of the applicability domain of the developed model. While the relative contribution and strength of each descriptor in the model was obtained by estimating the variation inflation factor, mean effect, and degree of contribution of each descriptor in the developed model. Model 3 which gave the best validation results was chosen as the best of the five models. This model dictates that the most important descriptors that influence the free radical scavenging activities of the hydrazone antioxidants are the Broto-Moreau autocorrelation - lag 2 / weighted by polarizabilities; Count of atom-type H E-State: H on C sp(3) bonded to saturated C; Number of hydrogen bond donors (using CDK H Bond Donor Count Descriptor algorithm); Structural information content index (neighborhood symmetry of 1-order) and the 3D topological distance based autocorrelation - lag 7 / weighted by I-state descriptors. The Structural information content index descriptor was observed to be the most influential of all the descriptors.