Synthesis and PGE2 production inhibition of s-triazine derivatives as a novel scaffold in RAW 264.7 macrophage cells |
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| Affiliation: | 1. Research Institute for Basic Sciences and Department of Chemistry, College of Sciences, Kyung Hee University, Seoul 130-701, Republic of Korea;2. Department of Life and Nanopharmaceutical Science, Kyung Hee University, 1 Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Republic of Korea;3. Reactive Oxygen Species Medical Research Center, School of Medicine, Kyung Hee University, Seoul 130-701, Republic of Korea;1. M. V. Lomonosov Moscow State University of Fine Chemical Technology, 119571 Moscow, Russian Federation;2. Photochemistry Center, Russian Academy of Sciences, 119421 Moscow, Russian Federation;3. N. M. Emanuel Institute of Biochemical Physics, Russian Academy of Sciences, 119334 Moscow, Russian Federation;1. Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;2. Pharmacology and Toxicology Division, National Institute of Pharmaceutical Education and Research (NIPER), Hyderabad 500 037, India;3. Division of Organic Chemistry, CSIR-Indian Institute of Chemical Technology, Hyderabad 500 007, India;1. College of Chemistry & Chemical Engineering, Jiangxi Normal University, Nanchang 330022, PR China;2. Key Laboratory of Functional Small Organic Molecule, Ministry of Education, Nanchang 330022, PR China |
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| 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. |
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| Keywords: | Inflammation Cyanuric chloride Isostere Docking study |
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