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HQSAR Study of Microsomal Prostaglandin E2 Synthase (mPGES-1) Inhibitors
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  • HQSAR Study of Microsomal Prostaglandin E2 Synthase (mPGES-1) Inhibitors
  • HQSAR Study of Microsomal Prostaglandin E2 Synthase (mPGES-1) Inhibitors
저자명
San Juan. Amor A.,Cho. Seung-Joo,Cho. Hoon
간행물명
Bulletin of the Korean Chemical Society
권/호정보
2006년|27권 10호|pp.1531-1536 (6 pages)
발행정보
대한화학회
파일정보
정기간행물|ENG|
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이 논문은 한국과학기술정보연구원과 논문 연계를 통해 무료로 제공되는 원문입니다.
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기타언어초록

Microsomal prostaglandin $E_2$ synthase (mPGES-1) is an enzyme that is associated with inflammation, pain, fever and cancer. Hologram quantitative structure activity relationship (HQSAR) was conducted on the series of MK-886 compounds acting as mPGES-1 inhibitors. A training set with 24 compounds was used to establish the HQSAR model. The best model was chosen based on the cross-validated correlation coefficient ($q^2$=0.884) and the correlation coefficient($r^2$=0.976). The model was utilized to predict the activity of the eight-test set of compounds giving the predictive $r^2$ value of 0.845. The descriptors of the model are based on fragment distinction (atoms, bond and connectivity) and fragment size (2-5 atoms). The atomic contribution maps generated from HQSAR were useful in identifying the important structural features responsible for the inhibitory activity of MK-886 inhibitors. Based on the generated model, the presence of hydrophobic biphenyl group seems to enhance inhibition of mPGES-1 that is in agreement with the previous experiments. In addition, it seems important for a halogen to be substituted to the biphenyl ring and for an acyl group to be attached to the indole moiety for enhanced activity.