상동성 모델링을 이용한 Tricyclic Isoxazole 유도체와 α2c-Adrenoceptor의 상호작용

• 영문명: Interactions of Tricyclic Isoxazole Analogues with α2c-Adrenoceptor by Homology Modeling
• 발행기관: 대한약학회
• 저자명: 최경섭(Kyoung-Seob Choi) 강나나(Na-na Kang) 명평근(Pyung-Keun Myung) 성낙도(Nack-Do Sung)
• 간행물 정보: 『약학회지』제54권 제4호 (2010년), 300~308쪽, 전체 9쪽
• 주제분류: 의약학 > 기타의약학
• 파일형태: PDF
• 발행일자: 2010.08.31

영문 초록

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 α2c-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 Å) and O (1.712 Å) 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 π-π interaction at 3.342 Å 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.

키워드

tricyclic isoxazoles adrenoreceptor homology modeling blood-brain distribution(logBB) polar surface area(PSA)