Suppressive effects of novel ferulic acid derivatives on cellular responses induced by phorbol ester, and by combined lipopolysaccharide and interferon-gamma

A total of 23 ferulic acid (FA) derivatives were synthesized, and investiga ted for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate-in duced Epstein-Barr virus (EBV) activation and superoxide (O-2(-)) generatio n. Most of the derivatives showed significant EBV activation suppression or cytotoxicity at a concentration of 100 muM, with FA15 as the most potent s uppressor. In both assays, FA6-FA17, bearing straight- or branched-alkyl si de chains, exhibited marked suppression of O-2(-) generation, with both FA1 6 and FA17 being highly active, while FA itself was virtually inactive. The activity differences seen between FA16/FA17 and FA are attributable, at le ast in part, to their cellular incorporating efficiencies. Further, both FA 15 and FA21 attenuated the expression of inducible nitric oxide synthase an d cyclooxygenase-2 proteins, while FA did not. Our results suggest that the se novel FA derivatives are effective chemopreventive agents. (C) 2000 Else vier Science Ireland Ltd. All rights reserved.