Synthesis of biflavones having a 6-O-7'' linkage and effects on cyclooxygenase-2 and inducible nitric oxide synthase.
In order to establish anti-inflammatory potential of biflavonoids, 17 biflavone derivatives having a 6-O-7'' linkage were synthesized and their effects on cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) were evaluated. The basic molecule (6-O-7'' biflavone) potently inhibited COX-2-mediated PGE(2) production (IC(50): <2 microM), being less active on iNOS-mediated NO production (IC(50): >50 microM) from lipopolysaccharide-treated RAW 264.7 cells, a mouse macrophage cell line. Generally, the hydroxyl/methoxyl substitution(s) on the basic biflavone (6-O-7'') reduced the inhibitory activity of PGE(2) production, while the effects on NO production were varied. It is suggested that the basic biflavone (6-O-7'') may have a potential for new anti-inflammatory agent.
Che
Haiyan
H
College of Pharmacy, Kangwon National University, Chunchon, Republic of Korea.
Park
Byung Kyu
BK
Lim
Hyun
H
Kim
Hyun Pyo
HP
Chang
Hyeun Wook
HW
Jeong
Jin-Hyun
JH
Park
Haeil
H
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis*; D044946:Biflavonoids / Q000138:chemical synthesis*; D002460:Cell Line; D052246:Cyclooxygenase 2 Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D047309:Flavones / Q000138:chemical synthesis; D020128:Inhibitory Concentration 50; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D052247:Nitric Oxide Synthase Type II / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D000893:Anti-Inflammatory Agents; D044946:Biflavonoids; D052246:Cyclooxygenase 2 Inhibitors; D047309:Flavones; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D015232:Dinoprostone