2. Academic Validation
  3. Synthesis and biological evaluation of novel 5-benzylidenethiazolidine-2,4-dione derivatives for the treatment of inflammatory diseases

Synthesis and biological evaluation of novel 5-benzylidenethiazolidine-2,4-dione derivatives for the treatment of inflammatory diseases

  • J Med Chem. 2011 Apr 14;54(7):2060-8. doi: 10.1021/jm1011534.
Liang Ma 1,  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
Affiliations

Affiliation

  • 1 State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
PMID: 21381754 DOI: 10.1021/jm1011534
Abstract

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 E(2) (PEG(2)). (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 (IC(50) = 8.66 μM), iNOS-mediated NO, and cyclooxygenase (COX)-2-derived PGE(2) production (IC(50) = 4.16 and 23.55 μM, 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.

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