Effect of ginger constituents and synthetic analogues on cyclooxygenase-2 enzyme in intact cells.
Seventeen pungent oleoresin principles of ginger (Zingiber officinale, Roscoe) and synthetic analogues were evaluated for inhibition of cyclooxygenase-2 (COX-2) enzyme activity in the intact cell. These compounds exhibited a concentration and structure dependent inhibition of the enzyme, with IC(50) values in the range of 1-25 microM. Ginger constituents, [8]-paradol and [8]-shogaol, as well as two synthetic analogues, 3-hydroxy-1-(4-hydroxy-3-methoxyphenyl)decane and 5-hydroxy-1-(4-hydroxy-3-methoxyphenyl)dodecane, showed strong inhibitory effects on COX-2 enzyme activity. The SAR analysis of these phenolic compounds revealed three important structural features that affect COX-2 inhibition: (i) lipophilicity of the alkyl side chain, (ii) substitution pattern of hydroxy and carbonyl groups on the side chain, and (iii) substitution pattern of hydroxy and methoxy groups on the aromatic moiety.
Tjendraputra
E
E
Herbal Medicines Research and Education Centre, University of Sydney, NSW 2006, Australia.
Tran
V H
VH
Liu-Brennan
D
D
Roufogalis
B D
BD
Duke
C C
CC
D002396:Catechols; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002627:Chemistry, Physical; D051546:Cyclooxygenase 2; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000187:drug effects / Q000201:enzymology; D005233:Fatty Alcohols / Q000737:chemistry / Q000494:pharmacology; D020939:Zingiber officinale / Q000737:chemistry*; D006801:Humans; D006900:Hydroxylation; D007527:Isoenzymes / Q000378:metabolism*; D008565:Membrane Proteins; D008956:Models, Chemical; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D013329:Structure-Activity Relationship
D002396:Catechols; D052246:Cyclooxygenase 2 Inhibitors; D016861:Cyclooxygenase Inhibitors; D005233:Fatty Alcohols; D007527:Isoenzymes; D008565:Membrane Proteins; C007845:gingerol; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases