Synthesis and Biological Evaluation of Novel 5-Benzylidenethiazolidine-2,4-dione Derivatives for the Treatment of Inflammatory Diseases

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• 作者：Liang Ma ; Caifeng Xie ; Yinghua Ma ; Juan Liu ; Mingli Xiang ; Xia Ye ; Hao Zheng ; Zhizhi Chen ; Qinyuan Xu ; Tao Chen ; Jinying Chen ; Jincheng Yang ; Neng Qiu ; Guangcheng Wang ; Xiaolin Liang ; Aihua Peng ; Shengyong Yang ; Yuquan Wei ; Lijuan Chen
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：April 14, 2011
• 年：2011
• 卷：54
• 期：7
• 页码：2060-2068
• 全文大小：962K
• 年卷期：v.54,no.7(April 14, 2011)
• ISSN：1520-4804

文摘

Twenty-two compounds based on thiazolidine-2,4-dione moiety were synthesized and evaluated for the inhibitory potency on the production of nitric oxide (NO), inducible nitric oxide synthase (iNOS) activity, and the generation of prostaglandin E₂ (PEG₂). (Z)-N-(3-Chlorophenyl)-2-(4-((2,4-dioxothiazolidin-5-ylidene) methyl) phenoxy) acetamide (3I), superior to the commercial anti-inflammatory drug indomethacin, significantly inhibited iNOS activity (IC₅₀ = 8.66 渭M), iNOS-mediated NO, and cyclooxygenase (COX)-2-derived PGE₂ production (IC₅₀ = 4.16 and 23.55 渭M, respectively) on lipopolysaccharide (LPS)-induced RAW 264.7 cells. Docking study revealed that 3I was perfectly docking into the active site of murine iNOS and suppressed the expression of iNOS protein as evidenced by Western blot analysis. At the dose of 50 mg/kg, oral administration of 3I possessed protective properties in both carrageenan-induced paw edema and adjuvant-induced arthritis rat models.