Quantum chemical reactivity descriptors such as molecular weight, heat of formation, total energy, HOMO energy, LUMO energy, absolute hardness and electronegativity have been used to develop QSAR model of the inhibitors of the enzyme, acetylcholinesterase, AchE. The inhibitors used are O-phosphorylated oxime derivatives. The inhibitory activities of various derivatives against the enzyme, acetylcholinesterase has been taken from literature. The values of various descriptors have been evaluated by using Win MOPAC 7.21 software with the help of PM3, PM5 and DFT methods. Thus three different methods have been employed to certify the reliability of QSAR study. Multiple linear regression analysis has been made with the help of above mentioned descriptors using the same software. Three different sets of regression equations are thus obtained corresponding to the three different methods. The first set of models has been drawn up with the help of PM3 calculations and the best model in this set having the correlation coefficient, r2 as 0.78 and the cross-validation coefficient, r2 cv as 0.60 has been chosen as the QSAR model. The second set of models has been drawn up with the help of PM5 calculations and the best model in this set having the correlation coefficient, r2 as 0.78 and the cross-validation coefficient, r2 cv as 0.63 has been chosen as the QSAR model. Finally, the third set of models has been developed with the help of DFT calculations for the same series of derivatives by using B88-PW91 GGA energy functional with the DZVP basis set. The best model by DFT method has correlation coefficient, r2 as 0.79 and cross-validation coefficient, r2 cv as 0.64 and so this has been chosen as the QSAR model for this method. The DFT models have a higher predictive power than PM3 and PM5 methods as evident from the regression parameters. Present study has also been helpful in developing a relationship between electronegativity and anticholinesterase activity of O-phosphorylated oxime derivatives which has never been studied before.
O-Phosphorylated oxime derivatives, QSAR, DFT, Acetylcholinesterase, Electronegativity