QUANTITATIVE STRUCTURE-ACTIVITY-RELATIONSHIPS OF CATECHOL DERIVATIVESON NERVE GROWTH-FACTOR SECRETION IN L-M CELLS

Purpose. Although many catechol derivatives are potent stimulators of Nerve Growth Factor synthesis in L-M cells, not much is known about th eir mechanism of action. In order to obtain a Quantitative Structure A ctivity Relationship (QSAR), AM1 quantum mechanical calculations were performed on a group of 23 catechol derivatives with different levels of activity. Methods. A set of 18 parameters/descriptors were obtained by AM1 quantum mechanical calculations for each catechol derivative. Linear combinations of the calculated descriptors were fitted to the a ctivity (as extracted from literature data) of the compounds by using simple or multiple regression analysis. Results. Good correlation with activity was obtained for specific parameters such as the adiabatic i onization potential and other 'oxidation'-related descriptors of the m olecules while poor correlation was observed for most of the other par ameters as, for example, for log P. Conclusions. Our results show that activity is associated with parameters related to the oxidation of th e catechol derivatives, strongly supporting recent literature suggesti ng that an oxidative process is involved in their action.