Novel conjugates of aspirin with phenolic acid as anti-inflammatory agents having significantly reduced gastrointestinal toxicity.
A series of novel conjugates of aspirin with natural phenolic acid antioxidants connected through a diol linker were designed and synthesized as potential bifunctional agents combining antioxidant and anti-inflammatory activity for reducing gastrointestinal toxicity. In general, the conjugates were found to be efficient antioxidants and many of them demonstrated much more potent anti-inflammatory activity than aspirin. Among them, 5a and 5b which bear the best anti-inflammatory activity exhibited significantly reduced ulcerogenic potency and toxicity compared to aspirin. However, it is evident that the anti-inflammatory activity of these dual-acting molecules in vivo, was not simply consistent with their antioxidant ability in vitro.
Jiang
Shan
S
School of Medicine and Pharmacy, Ocean University of China, Qingdao, PR China.
Ding
Ning
N
Zhang
Wei
W
Zhang
Yichun
Y
Geng
Meiyu
M
Li
Yingxia
Y
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001241:Aspirin / Q000031:analogs & derivatives / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D001713:Biphenyl Compounds / Q000737:chemistry; D003436:Croton Oil; D004195:Disease Models, Animal; D015195:Drug Design; D062385:Hydroxybenzoates / Q000138:chemical synthesis / Q000494:pharmacology* / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010851:Picrates / Q000737:chemistry; D013276:Stomach Ulcer / Q000139:chemically induced / Q000378:metabolism / Q000517:prevention & control*; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D001713:Biphenyl Compounds; D062385:Hydroxybenzoates; D010851:Picrates; D003436:Croton Oil; C004931:1,1-diphenyl-2-picrylhydrazyl; C017616:phenolic acid; D001241:Aspirin