Synthesis, anti-inflammatory, and antioxidant activities of 18beta-glycyrrhetinic acid derivatives as chemical mediators and xanthine oxidase inhibitors.
Twenty 18beta-glycyrrhetic acid (18beta-GA) derivatives 2-21 including 13 new 18beta-GA derivatives were synthesized and evaluated as anti-inflammatory and antioxidant agents. Compounds 7 and 20 with a 3,4-seco-structure and compound 6 with a lactone moiety showed potent inhibitory effect on superoxide anion generation in rat neutrophils response to fMLP/CB and PMA, respectively. Compound 6 with a lactone moiety revealed stronger inhibitory effect on XO activity than those of compounds 13 and 14 with a 3,4-seco-structure. Compound 14, a 30-isoproylcarbamoyl seco-compound exhibited potent inhibitory effect on NO accumulation and iNOS protein expression while compounds 3, 10, 13, 15, 17, and 21 revealed potent inhibitory effect on tumor necrosis factor-alpha (TNF-alpha) formation in RAW 264.7 cells in response to lipopolysaccharide (LPS). The cleavage of ring A of 3 attenuated the inhibitory effect on TNF-alpha formation in RAW 264.7 cells in response to LPS except for 17. The present results suggested these compounds were potential to be served as anti-inflammatory and antioxidant agents.
Maitraie
Dravidum
D
Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Hung
Chi-Feng
CF
Tu
Huang-Yao
HY
Liou
Ya-Ting
YT
Wei
Bai-Luh
BL
Yang
Shyh-Chyun
SC
Wang
Jih-Pyang
JP
Lin
Chun-Nan
CN
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000975:Antioxidants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006034:Glycyrrhetinic Acid / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000378:metabolism; D051379:Mice; D009504:Neutrophils / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D013481:Superoxides / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D014969:Xanthine Oxidase / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D013481:Superoxides; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D014969:Xanthine Oxidase; D006034:Glycyrrhetinic Acid