A Kourounakis1, N Bodor. 1. Center for Drug Discovery, College of Pharmacy, University of Florida, Gainesville 32610-0497, USA.
Abstract
PURPOSE: Although many catechol derivatives are potent stimulators of Nerve Growth Factor synthesis in L-M cells, not much is known about their mechanism of action. In order to obtain a Quantitative Structure Activity 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 activity (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 ionization potential and other 'oxidation'-related descriptors of the molecules while poor correlation was observed for most of the other parameters as, for example, for log P. CONCLUSIONS: Our results show that activity is associated with parameters related to the oxidation of the catechol derivatives, strongly supporting recent literature suggesting that an oxidative process is involved in their action.
PURPOSE: Although many catechol derivatives are potent stimulators of Nerve Growth Factor synthesis in L-M cells, not much is known about their mechanism of action. In order to obtain a Quantitative Structure Activity 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 activity (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 ionization potential and other 'oxidation'-related descriptors of the molecules while poor correlation was observed for most of the other parameters as, for example, for log P. CONCLUSIONS: Our results show that activity is associated with parameters related to the oxidation of the catechol derivatives, strongly supporting recent literature suggesting that an oxidative process is involved in their action.
Authors: K Kaechi; Y Furukawa; R Ikegami; N Nakamura; F Omae; Y Hashimoto; K Hayashi; S Furukawa Journal: J Pharmacol Exp Ther Date: 1993-01 Impact factor: 4.030