DFT-based QSAR study of valproic acid and its derivatives

The usefulness of the quantum chemical descriptors, calculated at the level of the DFT theory using 6-31G (d) basis set for QSAR study of antiepileptic drugs was examined. A dataset containing 25 valproic acid derivatives with known activity was used. Three types of molecular descriptors including AIM, chemical and quantum chemical was used to derive a quantitative relationship between the antiepileptic activity and structural properties. Multiple linear regressions were employed to model the relationships between molecular descriptors and biological activity of molecules using stepwise method and genetic algorithm as variable selection tools. A multi-parametric equation containing three descriptors with good statistical qualities was obtained by Multiple Linear Regression (MLR) using stepwise method. Also, GA-MLR regression was used to model the structure-activity relationships more accurately. The results showed that the results obtained by GA-MLR are similar to MLR