Effect of ginger constituents and synthetic analogues on cyclooxygenase-2 enzyme in intact cells

Seventeen pungent oleoresin principles of ginger (Zingiber officinale, Rosc oe) 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 IC50 v alues in the range of 1-25 muM. Ginger constituents, [8]-paradol and [8]-sh ogaol, as well as two synthetic analogues, 3-hydroxy-1-(4-hydroxy-3-methoxy phenyl)decane and 5-hydroxy-1-(3-hydroxy-3-methoxyphenyl)dodecane,showed st rong inhibitory effects on COX-2 enzyme activity. The SAR analysis of these phenolic compounds revealed three important structural features that affec t COX-2 inhibition: (i) lipophilicity of the alkyl side chain, (ii) substit ution pattern of hydroxy and carbonyl groups on the side chain, and (iii) s ubstitution pattern of hydroxy and methoxy groups on the aromatic moiety, ( C) 2001 Academic Press.