Synthesis and biological evaluation of novel dimethyl[1,1'-biphenyl]-2,2'-dicarboxylate derivatives containing thiazolidine-2,4-dione for the treatment of concanavalin A-induced acute liver injury of BALB/c mice.
In this paper, we reported the synthesis of bifendate derivatives and evaluation of anti-inflammatory activity by detecting the production of the Nitric Oxide (NO) in the lipopolysaccharide(LPS)-stimulated RAW 264.7 cell lines. Among the newly derivatives, compound 7k was the most potent one and two other compounds (7e and 7f) also exhibited greater anti-inflammatory activity than bifendate. Further in vivo studies confirmed that 7k significantly and dose-dependently inhibited carrageenan-induced paw edema and decreased the serum levels of alanine aminotransaminase, and aspartate aminotransaminase in concanavalin A-induced hepatitis model. Histopathological evaluation demonstrated that 7k has better hepatoprotective effect on acute liver injury induced by concanavalin A than bifendate, suggesting that 7k is a potential drug candidate for the treatment of hepatic injuries.
State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Keyuan Road 4, Gaopeng Street, Chengdu 610041, People's Republic of China.
Guangcheng
G
Wang
Chongyang
C
Deng
Caifeng
C
Xie
Liang
L
Ma
Jincheng
J
Yang
Neng
N
Qiu
Qinyuan
Q
Xu
Tao
T
Chen
Fei
F
Peng
Jinying
J
Chen
Jingxiang
J
Qiu
Aihua
A
Peng
Yuquan
Y
Wei
Lijuan
L
Chen
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D003208:Concanavalin A; D004487:Edema / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D005260:Female; D006520:Hepatitis, Animal / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008070:Lipopolysaccharides / Q000276:immunology; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000276:immunology; D051381:Rats
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001713:Biphenyl Compounds; D008070:Lipopolysaccharides; C465548:bifendate; D003208:Concanavalin A; D009569:Nitric Oxide