1. Discovery of a novel inhibitor of nitric oxide production with potential therapeutic effect on acute inflammation.
- Author
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Zhu LQ, Fan XH, Li JF, Chen JH, Liang Y, Hu XL, Ma SM, Hao XY, Shi T, and Wang Z
- Subjects
- Acute Disease, Amides chemical synthesis, Amides chemistry, Animals, Anti-Inflammatory Agents, Non-Steroidal chemical synthesis, Anti-Inflammatory Agents, Non-Steroidal chemistry, Bridged Bicyclo Compounds chemical synthesis, Bridged Bicyclo Compounds chemistry, Carrageenan, Dose-Response Relationship, Drug, Edema chemically induced, Edema drug therapy, Inflammation metabolism, Lipopolysaccharides antagonists & inhibitors, Lipopolysaccharides pharmacology, Mice, Molecular Structure, Nitric Oxide biosynthesis, RAW 264.7 Cells, Structure-Activity Relationship, Amides pharmacology, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Bridged Bicyclo Compounds pharmacology, Drug Discovery, Inflammation drug therapy, Nitric Oxide antagonists & inhibitors
- Abstract
Inflammation as a host's excessive immune response to stimulation, is involved in the development of numerous diseases. To discover novel anti-inflammatory agents and based on our previous synthetic work on marine natural product Chrysamide B, it and a series of derivatives were synthesized and evaluated for their anti-inflammatory activity on inhibition of LPS-induced NO production. Then the preliminary structure-activity relationships were conducted. Among them, Chrysamide B is the most potent anti-inflammatory agent with low cytotoxicity and strong inhibition on the production of NO (IC
50 = 0.010 μM) and the activity of iNOS (IC50 = 0.082 μM) in LPS-stimulated RAW 264.7 cells. Primary studies suggested that the mechanism of action may be that it interfered the formation of active dimeric iNOS but not affected transcription and translation. Furthermore, its good performance of anti-inflammatory effect on LPS-induced multiple inflammatory cytokines production, carrageenan-induced paw edema, and endotoxin-induced septic mice, was observed. We believe that these findings would provide an idea for the further modification and research of these analogs in the future., (Copyright © 2021 Elsevier Ltd. All rights reserved.)- Published
- 2021
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