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Synthesis and biological evaluation of pyranoisoflavone derivatives as anti-inflammatory agents.

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机构: [1]State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China [2]Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China
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关键词: Tumor necrosis factor α Inflammatory Pyranoisoflavone TACE mRNA

摘要:
In this paper, barbigerone (1a) and its twenty-seven related structural analogues were synthesized via complementary synthetic routes and their anti-inflammatory effects on the expression of TNF-α in LPS-stimulated splenocytes were evaluated. Among these compounds, 1a, 1d, 1f and 1g were found to remarkably inhibit TNF-α production. Furthermore, 1g showed the most potent and dose-dependent manner inhibitory effect on TNF-α release, with better IC50 value (3.58 μM) than barbigerone (8.46 μM). Oral administration of 1g at 20 mg/kg/day for two weeks obviously demonstrated protective effect in adjuvant-induced arthritis models as evaluated by clinical score of paws, and histological examination of joint tissues from rats. Mechanism studies on mRNA and protein level suggested that 1g inhibited the TNF-α production via depressing TNF-α converting enzyme (TACE) mRNA expression. In conclusion, these data show 1g with potential therapeutic effects as an anti-inflammatory agent. Copyright © 2014 Elsevier B.V. All rights reserved.

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出版当年[2014]版:
大类 | 4 区 医学
小类 | 4 区 药物化学 4 区 药学
最新[2023]版:
大类 | 3 区 医学
小类 | 3 区 药物化学 3 区 药学
第一作者:
第一作者机构: [1]State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China
通讯作者:
通讯机构: [1]State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China [2]Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China [*1]No. 9 Section 4, Renmin Nan Road, Chengdu, Sichuan, PR China [*2]State Key Laboratory of Biotherapy,West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, PR China
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