Discovery of novel sesquistilbene indanone analogues as potent anti-inflammatory agents

• Published in: European journal of medicinal chemistry 2016-05, Vol.113, p.63-74
• Main Authors: Tang, Mei-Lin, Zhong, Chen, Liu, Zheng-Yu, Peng, Peng, Liu, Xin-Hua, Sun, Xun
• Format: Article
• Language: English
• Subjects: Animals; Anti-inflammatory; Anti-Inflammatory Agents, Non-Steroidal - chemical synthesis; Anti-Inflammatory Agents, Non-Steroidal - chemistry; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Cell Survival - drug effects; Cells, Cultured; Dose-Response Relationship, Drug; Drug Discovery; Female; Indanone; Indans - chemical synthesis; Indans - chemistry; Indans - pharmacology; Lipopolysaccharides - antagonists & inhibitors; Lipopolysaccharides - pharmacology; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred Strains; Models, Molecular; Molecular Structure; Nitric Oxide - antagonists & inhibitors; Nitric Oxide - biosynthesis; Stilbenes - chemical synthesis; Stilbenes - chemistry; Stilbenes - pharmacology; Structure-Activity Relationship; TLR4/JNK/NF-κB
• ISSN: 0223-5234; 1768-3254
• DOI: 10.1016/j.ejmech.2016.02.021

To develop novel anti-inflammatory agents with improved pharmaceutical profiles, twenty-eight novel sesquistilbene indanone analogues were synthesized and evaluated for anti-inflammatory activity using RAW264.7 cells. Among these compounds, compound 11k was found to be one of the most potent analogues in inhibiting NO production in LPS-stimulated RAW264.7 cells. Furthermore, it could also significantly suppress LPS-induced iNOS and COX-2 expression and NO production through TLR4/JNK/NF-κB signaling pathway in a concentration dependent manner. Sesquistilbene indanone analogue 11k was much more potent than resveratrol for its anti-inflammatory activity. It could also significantly suppress LPS-induced iNOS and COX-2 expression and NO production through TLR4/JNK/NF-κB signaling pathway in a concentration dependent manner. [Display omitted] •Compound 11k was more effective than resveratrol.•(±)-11k, (+)-11k and (−)-11k, do not have impacts on activity and toxicity.•(±)-11k could suppress iNOS, COX-2 expression and NO production.•The mechanism of (±)-11k was through TLR4/JNK/NF-κB signaling pathway.