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3D-QSAR Analysis on Antidepressant Activity of Tricyclic Isoxazole Analogues against Medetomidine-induced Loss of Righting  

Choi, Min-Sung (Sky Solution Inc., Business Incubation Center, Chungnam National University)
Sung, Nack-Do (Sky Solution Inc., Business Incubation Center, Chungnam National University)
Myung, Pyung-Keun (College of Pharmacy, Chungnam National University)
Publication Information
YAKHAK HOEJI / v.55, no.2, 2011 , pp. 98-105 More about this Journal
Abstract
To search the minimum structural requirement of tricyclic isoxazole analogues (1~30) as new class potent antidepressant, thee-dimensional quanti- tative-structure relationship (3D-QSAR) models between substituents ($R_1{\sim}R_5$) of tricyclic isoxazoles and their antidepressant activity against medetomidine-induced loss of righting were performed and discussed quantitatively using comparative molecular field analysis (CoMFA) and comparative molecular similarity indies analysis (CoMSIA) methods. The correlativity and predictability ($r^2$=0.484 and $q^2$=0.947) of CoMSIA-2 model were higher than those of the rest models. The inhibitory activity against medetomidine-induced loss of righting was dependent on electrostatic field (43.4%), hydrophobic field (35.3%), and steric field (21.2%) of tricyclic isoxazoles. From the CoMSIA-2 contour maps, it is predicted that the antidepressant activity of potent antidepressants against medetomidine-induced loss of righting will be able to increase by the substituents ($R_1{\sim}R_5$) which were in accord with CoMSIA field.
Keywords
tricyclic isoxazoles; medetomidine-induced loss of righting; antidepressant activity; 3D-QSAR;
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