新型吡唑啉衍生物作为强效抗炎剂的合成及生物学评价
Synthesis and biological evaluation of novel pyrazoline derivatives as potent anti-inflammatory agents.
作者信息
He Jiqiang, Ma Liang, Wei Zhe, Zhu Jun, Peng Fei, Shao Mingfeng, Lei Lei, He Lin, Tang Minghai, He Linhong, Wu Yuzhe, Chen Lijuan
机构信息
State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, and Collaborative Innovation Center for Biotherapy, Chengdu 610041, China.
Chemistry College, Sichuan University, Chengdu, Sichuan 610064, China.
出版信息
Bioorg Med Chem Lett. 2015 Jun 1;25(11):2429-33. doi: 10.1016/j.bmcl.2015.03.087. Epub 2015 Apr 3.
Twenty-eight pyrazoline derivatives, which originated from pyranochalcones, have been synthesized and evaluated for their inhibitory potency on the production of inflammatory mediator nitric oxide (NO) in LPS-stimulated RAW 264.7 cells. Among them, three compounds (1c, 11c, and 15c) exhibited potent inhibitory effects on NO production and iNOS activity superior to positive control Indomethacin, with 1c being most efficacious. Furthermore, 1c could suppress the progress of carrageenan-induced hind paw edema at a dosage of 50 mg/kg/day and dose-dependently ameliorate the development of adjuvant-induced arthritis (AIA). Docking study confirmed that 1c was an iNOS inhibitor with good binding into the active site of murine iNOS.
已合成了28种源自吡喃查耳酮的吡唑啉衍生物，并评估了它们对脂多糖刺激的RAW 264.7细胞中炎症介质一氧化氮（NO）产生的抑制效力。其中，三种化合物（1c、11c和15c）对NO产生和诱导型一氧化氮合酶（iNOS）活性表现出强效抑制作用，优于阳性对照吲哚美辛，其中1c最为有效。此外，1c在剂量为50 mg/kg/天时可抑制角叉菜胶诱导的后爪水肿进展，并剂量依赖性地改善佐剂诱导的关节炎（AIA）的发展。对接研究证实，1c是一种iNOS抑制剂，能很好地结合到小鼠iNOS的活性位点。
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