Characterization of xanthine oxidase inhibition by anacardic acids

Anacardic acid, 6[8(Z), 11(Z), 14-pentadecatrienyl]salicylic acid, inhibits generation of superoxide radicals by xanthine oxidase. This inhibition does not follow a hyperbolic inhibition, depends on anacardic acid concentrations, but follows a sigmoidal inhibition. The inhibition was analyzed by using a Hill equation, and slope factor and EC50 were 4.3 +/- 0.5 and 53.6 +/- 5.1 muM, respectively. In addition, anacardic acid inhibited uric acid formation by xanthine oxidase cooperatively. Slope factor and EC50 were 1.7 +/- 0.5 and 162 +/- 10 muM, respectively. The results indicate that anacardic acid binds to allosteric sites near the xanthine-binding domain in xanthine oxidase. Salicylic acid moiety and alkenyl side chain in anacardic acid are associated with the cooperative inhibition and hydrophobic binding, respectively. (C) 2004 Elsevier B.V. All rights reserved.