HQSAR Analyses on the Tyrosinase Inhibitory Activity of Phenyl-2,2'-methylenebis(cyclohexane-1,3-dione) Analogues

Phenyl-2,2'-methylenebis(cyclohexane-1,3-dione) 유도체의 Tyrosinase 저해활성에 관한 HQSAR 분석

  • Kim, Sang-Jin (Department of Cosmetic Science, Daejeon Health Sciences College) ;
  • Kim, Young-Ok (Chemolee Lab Corporation R&D Center) ;
  • Cho, Yoon-Ki (Sky Solution Inc. R&D Center) ;
  • Choi, Won-Seok (Department of Applied Biology and Chemistry, Chungnam National University) ;
  • Sung, Nack-Do (Department of Applied Biology and Chemistry, Chungnam National University)
  • 김상진 (대전보건대학 화장품과학과) ;
  • 김영옥 (케모리랩 연구소) ;
  • 조윤기 (스카이솔류션(주) 연구소) ;
  • 최원석 (충남대학교 응용생물화학과) ;
  • 성낙도 (충남대학교 응용생물화학과)
  • Received : 2010.08.22
  • Accepted : 2010.09.10
  • Published : 2010.09.30


The structure-activity relationships (SARs) between a series of phenyl-2,2'-methylenebis(cyclohexane-1,3-dione) analogues (1-22) as substrate molecules and their inhibitory activity against tyrosinase were studied quantitatively using molecular hologram quantitative structure-activity relationships (HQSARs). Based on the results, new compounds with the increased tyrosinase inhibitory activity were designed. In addition, statistically favored E-2 model ($q_2$ = 0.564 & $r_2$ = 0.929) was derived. It is predicted that the activity of the most potent one (P1) of compounds newly designed by the optimized HQSAR E-2 model was $Pred.pI_{50}$ = 5.48 and the predicted inhibitory activity was about 13.4 fold higher than that of the kojic acid used as standard compound.

기질 화합물로써 일련의 phenyl-2,2'-methylenebis(cyclohexane-1,3-dione) 유도체(1-22)들의 치환기($R_1$$R_2$)가 변화함에 따른 tyrosinase 활성저해에 대한 분자 홀로그래피적인 정량적 구조-활성관계(HQSAR) 모델을 유도하였다. 그리고 tyrosinase 저해활성에 미치는 구조상 요소들의 분석결과에 근거하여 높은 tyrosinase 저해활성을 보이는 새로운 tyrosinase 저해활성 분자를 설계하였다. 또한, 통계적으로 양호한 E-2 모델(상관성; $r_2$ = 0.929 및 예측성; $q_2$ = 0.564)을 유도하였으며 설계된 화합물, P1 ($Pred.pI_{50}$ = 5.48)는 기준물질로 사용된 kojic acid에 비하여 약 13.4배 높은 저해활성을 나타낼 것으로 예측되었다.



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