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.
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Authors | Tae Woo Kim, Yeonjoong Yong, Soon Young Shin, Hyeryoung Jung, Kwan Ha Park, Young Han Lee, Yoongho Lim, Kang-Yeoun Jung |
Journal | Bioorganic chemistry
(Bioorg Chem)
Vol. 59
Pg. 1-11
(Apr 2015)
ISSN: 1090-2120 [Electronic] United States |
PMID | 25658192
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2015 Elsevier Inc. All rights reserved. |
Chemical References |
- Anti-Inflammatory Agents, Non-Steroidal
- Triazoles
- Tumor Necrosis Factor-alpha
- Xylenes
- Cyclooxygenase 2
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Topics |
- Animals
- Anti-Inflammatory Agents, Non-Steroidal
(chemical synthesis, chemistry, therapeutic use)
- Cyclooxygenase 2
(immunology)
- Ear
(pathology)
- Edema
(chemically induced, drug therapy, immunology, pathology)
- Male
- Mice
- Molecular Docking Simulation
- Molecular Structure
- Structure-Activity Relationship
- Triazoles
(chemical synthesis, chemistry, therapeutic use)
- Tumor Necrosis Factor-alpha
(immunology)
- Xylenes
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