Quantitative Activity Structure Relationship (QSAR) of a Series of Azetidinones Derived from Dapsone by the Method of Density Functional Theory (DFT)

Abstract

This QSAR study, which involved a series of Azetidinones derived from 4,4'-diaminodiphenylsulfone (dapsone), yielded two models based on molecular descriptors and the antibacterial activities Escherichia coli and Staphylococcus aureus.The molecular descriptors were obtained by applying the methods of quantum chemistry at the B3LYP/6-31G (d) level. The statistical indicators of the first model which is a function of the Escherichia coli activity are: the coefficient of determination R<sup>2</sup> equals 0.992, the standard deviation S equals 0.342, the Fischer coefficient F equals 185.088 and the cross-validation coefficient Q<sup>2</sup><sub>CV</sub> equals 0.992. Those of the second model showing the activity of Staphylococcus aureus are: the regression coefficient R<sup>2</sup>= 0.987, a standard deviation S=0.193, the Fischer coefficient F=114.955 and the cross-validation coefficient Q<sup>2</sup><sub>CV</sub>= 0.987. These models have good statistical performances. The quantum descriptors of dipole moment (μ), global softness (σ) and electronegativity (χ) are responsible of the antibacterial activity of the Azetidinones derived from dapsone. In addition, the dipole moment is the priority descriptor for the prediction of the antibacterial activity of the studied compounds. The Eriksson et al. acceptance criteria used for the test set is verified. The values of the dtheo/dexp ratio of the theoretical and experimental activities for the test set tend towards unity.