title: Synthesis, anti-inflammatory, and antioxidant activities of 18beta-glycyrrhetinic acid derivatives as chemical mediators and xanthine oxidase inhibitors.
abstract: 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.
authors.affiliation: Faculty of Pharmacy, College of Pharmacy, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: Dravidum
authors.initials: D
authors.lastname: Maitraie
authors.forename: Chi-Feng
authors.initials: CF
authors.lastname: Hung
authors.forename: Huang-Yao
authors.initials: HY
authors.lastname: Tu
authors.forename: Ya-Ting
authors.initials: YT
authors.lastname: Liou
authors.forename: Bai-Luh
authors.initials: BL
authors.lastname: Wei
authors.forename: Shyh-Chyun
authors.initials: SC
authors.lastname: Yang
authors.forename: Jih-Pyang
authors.initials: JP
authors.lastname: Wang
authors.forename: Chun-Nan
authors.initials: CN
authors.lastname: Lin
mesh_terms: 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
chemical_list: 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