A NOVEL ANTIOXIDANT FLAVONOID (IDB-1031) AFFECTING MOLECULAR MECHANISMS OF CELLULAR ACTIVATION

In searching for new drug candidates which could help bridge the gaps between free radical oxidations, pathophysiological responses, and pharmacological treatment, a series of flavonoids was screened. The most interesting compound emerging from this screening, the flavone 3'-hydroxyfarrerol (IdB 1031), is presented in this article. This compound is a good inhibitor of microsomal lipid peroxidation induced by either iron-adenosine 5'-diphosphate (ADP) or carbon tetrachloride. The elevated rate constant for the interaction with peroxyl radicals, analysed by the kinetics of inhibition of crocin bleaching in the presence of a diazo initiator, gives an account for the observed antioxidant capacity. When tested on human neutrophils activated by fMLP, IdB 1031 inhibits (ID50:20 mu M) respiratory burst. This effect, which is possibly linked to the observed inhibition of protein-kinase C (ID50:50 mu M), seems rather specific since IdB 1031 does not inhibit tyr-kinases and casein-kinase-2, while Quercetin and other flavonoids inhibit unspecifically all these enzymes. These effects, as a whole, depict this compound as a drug candidate for diseases in which peroxidative damage is associated with the induction of inflammatory responses and specifically with activation of a respiratory burst of leucocytes.