YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
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3D-QSAR Analysis on Antidepressant Activity of Tricyclic Isoxazole Analogues against Medetomidine-induced Loss of Righting

Medetomidine에 유발된 정좌반사소실에 대한 Tricyclic Isoxazole 유도체들의 항우울성에 관한 3D-QSAR 분석

  • 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)
  • Received : 2010.08.27
  • Accepted : 2011.04.08
  • Published : 2011.04.30
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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

References

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