A QSAR Study on Neurotrophic Activities of N-p-Tolyl/phenylsulfonyl L-Amino Acid Thiolester Derivatives

The objective of the present work was to study the quantitative structure-activity relationship (QSAR) of the protective effects of N-p-tolyl/phenyl sulfonyl L-amino acid thiolester derivatives on anoxic damage of rat pheochromocytoma (PC12) cells. Four molecular parameters of seventeen N-p-tolyl/phenyl sulfonyl L-amino acid thiolester derivatives, including heat of formation, dipole moment, the energy of the highest occupied molecular orbital and the energy of the lowest unoccupied molecular orbital, were calculated with two semi-empirical quantum mechanical methods, PM6 and RM1, respectively. The QSAR model based on molecular parameters and protective effects of these compounds on anoxic damage of PC12 cells were studied using the multiple linear regression analysis and principal component analysis. It is found that dipole moment and the energy of the lowest unoccupied molecular orbital are important factors for neurotrophic activities of these N-p-tolyl/phenyl sulfonyl L-amino acid thiolester derivatives. Results from PM6 and RM1 methods were compared, indicating that using PM6 method to calculate these molecular parameters is probably more applicable to the QSAR analysis in this study.