Rational design, synthesis, and pharmacological properties of pyranochalcone derivatives as potent anti-inflammatory agents

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• 作者：Fei Peng^a ; ¹ ; Guangcheng Wang^a ; ¹ ; Xiuxia Li^a ; Dong Cao^a ; Zhuang Yang^b ; Liang Ma^a ; Haoyu Ye^a ; Xiaolin Liang^a ; Yan Ran^c ; Jinying Chen^a ; Jingxiang Qiu^a ; Caifeng Xie^a ; Chongyang Deng^a ; Mingli Xiang^a ; Aihua Peng^a ; Yuquan Wei^a ; Lijuan Chen^a ; ^{lijuan170@hotmail.com}
• 关键词：Anti-inflammation ; NO production ; iNOS ; Paw edema ; Pyranochalcones ; Adjuvant-induced arthritis
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2012
• 出版时间：August, 2012
• 年：2012
• 卷：54
• 期：Complete
• 页码：272-280
• 全文大小：1051 K

文摘

24 derivatives (5a-x) derived from natural pyranochalcones (I and II) were designed and evaluated for their inhibitory potency on the production of nitric oxide (NO) in LPS-stimulated RAW264.7 cells. Among them, four compounds (5b, 5d, 5f, and 5h) exhibited more potent inhibitory effects on iNOS activity and iNOS-mediated NO production than a positive control indomethacin. Furthermore, 5b could significantly suppress the progression of carrageenan-induced hind paw edema compared to indomethacin at a dosage of 10?mg/kg/day, and dose-dependently ameliorated the development of adjuvant-induced arthritis (AIA) validated by arthritic scores and H&E staining of joints. In addition, docking study confirmed that 5b was an iNOS inhibitor with binding to the active site of murine iNOS.