title: Investigation into potent inflammation inhibitors from traditional Chinese medicine.
abstract: Microsomal prostaglandin E synthase-1 (mPGES-1) is the key enzyme for prostaglandin E2 (PGE2) generation during inflammation and is a potential target for designing anti-inflammatory drugs. Potential inhibitors of m-PGES-1 were selected from traditional Chinese medicine (TCM Database@Taiwan) based on the pharmacophore map generated by the top HypoGen hypothesis and validated using structure- and ligand-based analysis. Key features for potential m-PGES-1 inhibitors include pi-interactions and H-bond donors. TCM compounds, shanciol B, shanciol A, castilliferol, and aurantiamide acetate, contoured to the quantitative structure-activity relationship pharmacophore and exhibited high docking scores and binding stability with m-PGES-1. Bioactivity models multiple linear regression (MLR) and support vector machine also supported activity predictions for the candidate compounds. Our results indicate that the investigated TCM compounds could be of use for development into mPGES-1 inhibitors.
authors.affiliation: Laboratory of Computational and Systems Biology, School of Chinese Medicine, China Medical University, Taichung 40402, Taiwan.
authors.forename: Kuan-Chung
authors.initials: KC
authors.lastname: Chen
authors.forename: Mao-Feng
authors.initials: MF
authors.lastname: Sun
authors.forename: Shun-Chieh
authors.initials: SC
authors.lastname: Yang
authors.forename: Su-Sen
authors.initials: SS
authors.lastname: Chang
authors.forename: Hsin-Yi
authors.initials: HY
authors.lastname: Chen
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Calvin Yu-Chian
authors.initials: CY
authors.lastname: Chen
mesh_terms: D000893:Anti-Inflammatory Agents / Q000737:chemistry* / Q000494:pharmacology*; D055808:Drug Discovery; D006801:Humans; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008516:Medicine, Chinese Traditional; D008861:Microsomes / Q000201:enzymology; D056004:Molecular Dynamics Simulation; D000071876:Prostaglandin-E Synthases; D011485:Protein Binding; D021281:Quantitative Structure-Activity Relationship; D060388:Support Vector Machine
chemical_list: D000893:Anti-Inflammatory Agents; D019746:Intramolecular Oxidoreductases; C000605862:PTGES protein, human; D000071876:Prostaglandin-E Synthases