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

  • Eur J Med Chem. 2012 Aug:54:272-80. doi: 10.1016/j.ejmech.2012.05.005.
Fei Peng  1 ,  Guangcheng Wang ,  Xiuxia Li ,  Dong Cao ,  Zhuang Yang ,  Liang Ma ,  Haoyu Ye ,  Xiaolin Liang ,  Yan Ran ,  Jinying Chen ,  Jingxiang Qiu ,  Caifeng Xie ,  Chongyang Deng ,  Mingli Xiang ,  Aihua Peng ,  Yuquan Wei ,  Lijuan Chen
Affiliations
  • 1. State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, China.
PMID: 22633833 DOI: 10.1016/j.ejmech.2012.05.005
Abstract

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.