Suppression of inducible nitric oxide synthase expression by yakuchinones and their analogues.
Analogues of yakuchinones were synthesized as inhibitors of nitric oxide production in lipopolysaccharide-activated macrophage cell line, RAW 264.7 cells. We prepared stronger inhibitors than the original natural molecules, yakuchinones A and B reported from Alpinia oxyphylla. From the limited structural activity relation study of analogues, we concluded that the optimal length of linker between two aryl groups and the presence of enone moiety in the linker were identified as essential for the activity. The IC50 value of the most potent structure was 0.92 microM. The active analogues suppressed the expression of inducible nitric oxide synthase protein and mRNA.
Lee
Hwa Jin
HJ
College of pharmacy, Sookmyung Women's University, Hyochangwoon-Gil, Seoul, Korea.
Kim
Ji Sun
JS
Yoon
Joung Wha
JW
Kim
Hee-Doo
HD
Ryu
Jae-Ha
JH
D032429:Alpinia / Q000737:chemistry; D000818:Animals; D015153:Blotting, Western; D002460:Cell Line; D036381:Diarylheptanoids / Q000138:chemical synthesis* / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D036381:Diarylheptanoids; D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II