Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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HQSAR Study of Microsomal Prostaglandin E2 Synthase (mPGES-1) Inhibitors

  • San Juan, Amor A. (Biochemicals Research Center, Korea Institute of Science and Technology) ;
  • Cho, Seung-Joo (Biochemicals Research Center, Korea Institute of Science and Technology) ;
  • Cho, Hoon (College of Engineering, Chosun University)
  • Published : 2006.10.20
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Abstract

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.

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