San Juan, Amor A. Cho, Seung Joo 2024-01-21T01:03:13Z 2024-01-21T01:03:13Z 2022-01-10 2007-05 1610-2940 https://pubs.kist.re.kr/handle/201004/134407 Microsomal prostaglandin E-2 synthase (mPGES-1) has been identified recently as a novel target for treating pain and inflammation. The aim of this study is to understand the binding affinities of reported inhibitors for mPGES-1 and further to design potential new mPGES-1 inhibitors. 3D-QSAR-CoMFA (comparative molecular field analysis) and CoMSIA (comparative molecular similarity indices analysis) - techniques were employed on a series of indole derivatives that act as selective mPGES-1 inhibitors. The lowest energy conformer of the most active compound obtained from systematic conformational search was used as a template for the alignment of 32 compounds. The models obtained were used to predict the activities of the test set of eight compounds, and the predicted values were in good agreement with the experimental results. The 3D-QSAR models derived from the training set of 24 compounds were all statistically significant (CoMFA; q(2) = 0.89, r(2) = 0.95, r(bs)(2) = 0.98, r(pred)(2) = 0.83 and CoMSIA; q(2) = 0.84, r(2) = 0.93, r(bs)(2) = 0.93, r(pred)(2) = 0.94). Contour plots generated for the CoMFA and CoMSIA models reveal useful clues for improving the activity of mPGES-1 inhibitors. In particular, substitutions of an electronegative fluorine atom or a bulky hydrophilic phenoxy group at the meta or para positions of the biphenyl rings might improve inhibitory activity. A plausible binding mode between the ligands and mPGES-1 is also proposed. English SPRINGER PARTIAL LEAST-SQUARES COMFA VALIDATION PROTEINS PATHWAY CELLS FIELD 3D-QSAR study of microsomal prostaglandin E-2 synthase (mPGES-1) inhibitors Article 10.1007/s00894-007-0172-0 1 JOURNAL OF MOLECULAR MODELING, v.13, no.5, pp.601 - 610 JOURNAL OF MOLECULAR MODELING 13 5 601 610 scie scopus 000246098500007 2-s2.0-34247892437 Biochemistry & Molecular Biology Biophysics Chemistry, Multidisciplinary Computer Science, Interdisciplinary Applications Biochemistry & Molecular Biology Biophysics Chemistry Computer Science Article PARTIAL LEAST-SQUARES COMFA VALIDATION PROTEINS PATHWAY CELLS FIELD 3D-QSAR drug design inflammation mPGES-1 pain