YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Interactions of Tricyclic Isoxazole Analogues with ${\alpha}_{2c}$-Adrenoceptor by Homology Modeling

상동성 모델링을 이용한 Tricyclic Isoxazole 유도체와 ${\alpha}_{2c}$-Adrenoceptor의 상호작용

  • Choi, Kyoung-Seob (Neotek Coperation) ;
  • Kang, Na-Na (College of Pharmacy, Chungnam National University) ;
  • Myung, Pyung-Keun (College of Pharmacy, Chungnam National University) ;
  • Sung, Nack-Do (Department of Applied Biological Chemistry, College of Agriculture & Life Science, Chungnam National University)
  • 최경섭 (네오텍(주)) ;
  • 강나나 (충남대학교 약학대학) ;
  • 명평근 (충남대학교 약학대학) ;
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학과)
  • Received : 2010.05.11
  • Accepted : 2010.07.16
  • Published : 2010.08.31
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Abstract

Adrenoceptor has been considered to be an important target in psychiatric disorders. Based on x-ray structures of bovine rhodopsin, we established homology model of ${\alpha}_{2c}$-adrenoceptor (ADA2C_rat) and then analyzed docking from binding model of receptor-ligand complex with high-active compound No.29 in tricyclic isoxazole analogues (1-30). We observed that the N (1.907 $\AA$) and O (1.712 $\AA$) atoms of isoxazole ring on the docked ligand (No.29) formed H-bonding interaction with O-H of Ser5.32 and carmeron phenyl ring centroid of tricyclic isoxazole formed $\pi-\pi$ interaction at 3.342 $\AA$ distance with phenyl ring centroid of Phe6.52. According to predictions of blood-brain distribution (logBB) through penetration of blood-brain barrie (BBB) and polar surface area (PSA) of the ligands, the high-active compound No.29 has values of logBB=-0.203, PSA=67.50, respectively. These results suggest that the high-active compound No.29 is a novel anti-depressant with the characteristics such as dopamine and serotonin.

Keywords

References

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