SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF 2'-HYDROXYCHALCONES AND FLAVONES AS INHIBITORS OF INFLAMMATORY MEDIATORS GENERATION

2'-Hydroxy-3,4-dimethoxy-3',4'-dimethylchalcone (3a), 2'-hydroxy-3',4',3,4-tetramethoxychalcone (3b), and their corresponding flavones, 3',4'-dimethoxy-7,8-dimethylflavone (4a) and 3',4',7,8-tetramethoxyflavone (4b), were prepared from 3,4-dimethoxycinnamic acid and the respective phenol. The four compounds inhibited enzymic lipid peroxidation and showed weak peroxyl scavenging activity. They also reduced LTB(4) release from human neutrophils stimulated by A23187. The chalcone 3b was the only compound able to inhibit in a concentration-dependent way, synovial human recombinant phospholipase A(2) activity, human platelet TXB(2) generation, and human neutrophil degranulation. This chalcone exerted topical antiinflammatory effects in mice.