Journal of the Society of Cosmetic Scientists of Korea (대한화장품학회지)

Society of Cosmetic Scientists of Korea (대한화장품학회)
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CoMFA Analysis on Inhibitory Effect of $3{\beta}$-Hydroxy-12-oleanen-28-oic Acid Analogues on PTP-1B Activity and Prediction of Active Compounds

$3{\beta}$-Hydroxy-12-oleanen-28-oic Acid 유도체들의 PTP-1B 저해활성에 대한 CoMFA 분석과 활성 분자들의 예측

  • Kim, Sang-Jin (Department of Cosmetic Science, Daejeon Health Sciences College) ;
  • Kim, Se-Gon (Division of Applied Biology and Chemistry, College of Agriculture and Life Science, Chungnam National University) ;
  • Sung, Nack-Do (Division of Applied Biology and Chemistry, College of Agriculture and Life Science, Chungnam National University)
  • 김상진 (대전보건대학 화장품과학과) ;
  • 김세곤 (충남대학교 농업생명과학대학 응용생물화학부) ;
  • 성낙도 (충남대학교 농업생명과학대학 응용생물화학부)
  • Published : 2008.06.30
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Abstract

The comparative molecular field analyses(CoMFA) models between the substituents with changing groups($R_1{\sim}R_4$) of $3{\beta}$-hydroxy-12-oleanen-28-oic acid derivatives as substrate molecule and their inhibitory activities($pI_{50}$) against protein tyrosine phosphatase(PTP)-1B were derived and discussed quantitatively. The optimized CoMFA F1 model have best predictability and fitness($r^2_{cv.}=0.654$ and $r^2_{ncv.}=0.995$). The order of contribution ratio (%) with CoMFA fields on the inhibitory activities was a steric field(53.0%), electrostatic field(36.2%) and hydrophobic field(10.8%). From the analytical results of CoMFA contour maps, the inhibitory activities were dependent on the R4 group in substrate molecules. Particularly, the new active compounds(P1 & P2) with the inhibitory activity against melanin synthesis were expected.

기질 화합물로써 $3{\beta}$-hydroxy-12-oleanen-28-oic acid 유도체들의 치환기($R_1{\sim}R_4$)가 변화함에 따른 protein tyrosine phosphatase(PTP)-1B의 저해활성에 관한 비교 분자장 분석(CoMFA) 모델을 유도하고 정량적으로 검토하였다. 최적의 CoMFA F1 모델은 가장 높은 예측성과 상관성($r^2_{cv.}=0.654$ 및 $r^2_{ncv.}=0.995$)을 나타내었다. 저해활성에 관한 CoMFA장 기여비율(%)의 순서는 입체장(53.0%), 정전기장(36.2%) 및 소수성장(10.8%) 이었다. 등고도 분석 결과로부터 저해활성은 기질 분자 내 $R_4$-치환기에 의존적이었으며 특히 melanin 저해활성이 높은 새로운 화합물(P1 및 P2)이 예측되었다.

Keywords

References

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