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Bioorg Chem. 2015 Apr;59:1-11. doi: 10.1016/j.bioorg.2015.01.003. Epub 2015 Jan 20.

Synthesis and biological evaluation of phenyl-1H-1,2,3-triazole derivatives as anti-inflammatory agents.

Author information

1
Department of Biochemical Engineering, Gangneung-Wonju National University, Gangwon 210-702, Republic of Korea.
2
Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea.
3
Department of Biological Sciences, Konkuk University, Seoul 143-701, Republic of Korea.
4
Department of Aquatic Life Medicine, Kunsan National University, Kunsan 573-701, Republic of Korea.
5
Division of Bioscience and Biotechnology, BMIC, Konkuk University, Seoul 143-701, Republic of Korea. Electronic address: yoongho@konkuk.ac.kr.
6
Department of Biochemical Engineering, Gangneung-Wonju National University, Gangwon 210-702, Republic of Korea. Electronic address: kyjung@gwnu.ac.kr.

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.

KEYWORDS:

Anti-inflammatory drug; COX-2; Diclofenac; In silico docking; NSAID; QSAR

PMID:
25658192
DOI:
10.1016/j.bioorg.2015.01.003
[Indexed for MEDLINE]

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