title: Synthesis and PGE₂ production inhibition of s-triazine derivatives as a novel scaffold in RAW 264.7 macrophage cells.
abstract: We present the synthesis and biological evaluation of a collection of s-triazine derivatives as a novel scaffold of compounds with the capability to inhibit the PGE₂ production in LPS-induced RAW 264.7 macrophage cells. A total of 12 derivatives were synthesized and assayed for PGE₂ reduction at 10 μM concentration. Two compounds (7b and 7i) exhibiting >90% inhibition of PGE₂ production were found to have IC₅₀ values of 5.76 and 5.52 μM, respectively. They were counter screened for inhibition on COX-2 activity in a cell free assay. Specifically, compound 7i (R¹ = 4-Bn-Ph, R² = Cl, R³ = Ph, R⁵ = CO₂Me) was highly active in cells while maintaining little COX-2 inhibition (∼0% at 10 μM). Molecular docking study provides the possibility that compound 7i could inhibit PGE₂ production by blocking the PGH₂ binding site of mPGES-1 instead of COX-2 enzyme. Based on this result, our synthetic efforts will focus on intensive structure-activity relationship (SAR) study of s-triazine scaffold to discovery a potential PGE₂ synthesis inhibitor.
authors.forename: Seoung Mook
authors.initials: SM
authors.lastname: Kang
authors.forename: Jinsung
authors.initials: J
authors.lastname: Lee
authors.forename: Jae Ho
authors.initials: JH
authors.lastname: Jin
authors.forename: Minju
authors.initials: M
authors.lastname: Kim
authors.forename: Sunhoe
authors.initials: S
authors.lastname: Lee
authors.forename: Hwi Ho
authors.initials: HH
authors.lastname: Lee
authors.forename: Ji-Sun
authors.initials: JS
authors.lastname: Shin
authors.forename: Kyung-Tae
authors.initials: KT
authors.lastname: Lee
authors.forename: Jae Yeol
authors.initials: JY
authors.lastname: Lee
mesh_terms: D000818:Animals; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000037:antagonists & inhibitors; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D051379:Mice; D000071876:Prostaglandin-E Synthases; D013329:Structure-Activity Relationship; D014227:Triazines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D014227:Triazines; D019746:Intramolecular Oxidoreductases; D000071876:Prostaglandin-E Synthases; C000605865:Ptges protein, mouse; D015232:Dinoprostone