title: Synthesis and biological evaluation of pyranoisoflavone derivatives as anti-inflammatory agents.
abstract: 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.
authors.affiliation: State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Zhe
authors.initials: Z
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China; Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China.
authors.forename: Youzhe
authors.initials: Y
authors.lastname: Yang
authors.affiliation: State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Caifeng
authors.initials: C
authors.lastname: Xie
authors.affiliation: State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Chunyan
authors.initials: C
authors.lastname: Li
authors.affiliation: State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Guangcheng
authors.initials: G
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Liang
authors.initials: L
authors.lastname: Ma
authors.affiliation: State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Mingli
authors.initials: M
authors.lastname: Xiang
authors.affiliation: Natural Products Research Center, Chengdu Institute of Biology, Chinese Academy of Sciences, Chengdu 610041, PR China. Electronic address: sunjian@cib.ac.cn.
authors.forename: Jian
authors.initials: J
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China.
authors.forename: Yuquan
authors.initials: Y
authors.lastname: Wei
authors.affiliation: State Key Laboratory of Biotherapy/and Collaborative Innovative Center of Biotherapy, West China Hospital, Sichuan University, Chengdu 610041, PR China. Electronic address: chenlijuan125@163.com.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Chen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D001169:Arthritis, Experimental / Q000188:drug therapy*; D002460:Cell Line; D002867:Chromones / Q000138:chemical synthesis* / Q000627:therapeutic use; D004353:Drug Evaluation, Preclinical; D005260:Female; D007529:Isoflavones / Q000138:chemical synthesis* / Q000627:therapeutic use; D008807:Mice, Inbred BALB C; D011917:Rats, Inbred Lew; D013329:Structure-Activity Relationship; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C000596995:3-(2',5'-dimethoxyphenyl)-8,8-dimethyl-4-oxo-4H,8H-benzo(1,2-b-3,4-b')dipyran; D000893:Anti-Inflammatory Agents; D002867:Chromones; D007529:Isoflavones; D014409:Tumor Necrosis Factor-alpha; C543999:barbigerone
keywords: Inflammatory; Pyranoisoflavone; TACE mRNA; Tumor necrosis factor α