Rational design, synthesis, and pharmacological properties of pyranochalcone derivatives as potent anti-inflammatory agents.
Rational design, synthesis, and pharmacological properties of pyranochalcone derivatives as potent anti-inflammatory agents.
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DOI：
10.1016/j.ejmech.2012.05.005
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发表时间：
2012-08
影响因子：
6.7
通讯作者：
Fei Peng;Guangcheng Wang;Xiuxia Li;Dong Cao;Zhuang Yang;Liang Ma;Haoyu Ye;X. Liang;Yan Ran;Jinying Chen;J. Qiu;Caifeng Xie;Chong-yang Deng;Mingli Xiang;A. Peng;Yuquan Wei;Li-juan Chen
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文献类型：
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作者：
Fei Peng;Guangcheng Wang;Xiuxia Li;Dong Cao;Zhuang Yang;Liang Ma;Haoyu Ye;X. Liang;Yan Ran;Jinying Chen;J. Qiu;Caifeng Xie;Chong-yang Deng;Mingli Xiang;A. Peng;Yuquan Wei;Li-juan Chen
设计了24个天然吡喃查尔酮衍生物（5a-x）（I和II），并评价了它们对LPS刺激的RAW 264.7细胞中一氧化氮（NO）产生的抑制效力。其中，四个化合物（5 b，5d，5 f，和5 h）表现出更有效的抑制作用iNOS活性和iNOS介导的NO生产比阳性对照吲哚美辛。此外，与10 mg/kg/天剂量的吲哚美辛相比，5 b可以显著抑制角叉菜胶诱导的后爪水肿的进展，并且通过关节炎评分和关节的H&E染色验证，剂量依赖性地改善抗炎剂诱导的关节炎（AIA）的发展。此外，对接研究证实，5 b是一种iNOS抑制剂，与小鼠iNOS的活性位点结合。
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.