title: Synthesis and biological evaluation of phenyl-1H-1,2,3-triazole derivatives as anti-inflammatory agents.
abstract: Rapid and efficient synthesis of a phenyl-1H-1,2,3-triazole library enabled cost-effective biological testing of a range of novel non-steroidal anti-inflammatory drugs with potential for improved drug efficacy and toxicity profiles. Anti-inflammatory activities of the phenyl-1H-1,2,3-triazole analogs synthesized in this report were assessed using the xylene-induced ear edema model in mice. At least four analogs, 2a, 2b, 2c, and 4a, showed more potent effects than the reference anti-inflammatory drug diclofenac at the same dose of 25 mg/kg. To explore relationships between the structural properties of phenyl-1H-1,2,3-triazole analogs and their anti-inflammatory activities in xylene-induced ear edema, comparative molecular field analysis was performed, and pharmacophores showing good anti-inflammatory activities were identified based on an analysis of contour maps obtained from comparative molecular field analysis. The anti-inflammatory effect on the molecular level was tested by the expression of tumor necrosis factor-alpha induced COX-2 using Western blots. Because the addition of the analog 2c caused the expression change of TNF-α induced COX-2, the molecular binding mode between 2c and COX-2 was elucidated using in silico docking.
authors: Department of Biochemical Engineering, Gangneung-Wonju National University, Gangwon 210-702, Republic of Korea.
authors: Tae Woo
authors: TW
authors: Kim
authors: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Yeonjoong
authors: Y
authors: Yong
authors: Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Soon Young
authors: SY
authors: Shin
authors: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Hyeryoung
authors: H
authors: Jung
authors: Department of Aquatic Life Medicine, Kunsan National University, Kunsan 573-701, Republic of Korea.
authors: Kwan Ha
authors: KH
authors: Park
authors: Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
authors: Young Han
authors: YH
authors: Lee
authors: Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: yoongho@konkuk.ac.kr.
authors: Yoongho
authors: Y
authors: Lim
authors: Department of Biochemical Engineering, Gangneung-Wonju National University, Gangwon 210-702, Republic of Korea. Electronic address: kyjung@gwnu.ac.kr.
authors: Kang-Yeoun
authors: KY
authors: Jung
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000276:immunology; D004423:Ear / Q000473:pathology; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000276:immunology / Q000473:pathology; D008297:Male; D051379:Mice; D062105:Molecular Docking Simulation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology; D014992:Xylenes
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014230:Triazoles; D014409:Tumor Necrosis Factor-alpha; D014992:Xylenes; D051546:Cyclooxygenase 2
keywords: Anti-inflammatory drug; COX-2; Diclofenac; In silico docking; NSAID; QSAR