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 microM) respiratory burst. This effect, which is possibly linked to the observed inhibition of protein-kinase C (ID50:50 microM), 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.
Department of Chemical Science and Technology, University of Udine, Italy.
F
F
Ursini
M
M
Maiorino
P
P
Morazzoni
A
A
Roveri
G
G
Pifferi
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002251:Carbon Tetrachloride / Q000494:pharmacology; D005419:Flavonoids / Q000494:pharmacology*; D006801:Humans; D007501:Iron / Q000494:pharmacology; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology; D010545:Peroxides / Q000378:metabolism; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D051381:Rats; D017207:Rats, Sprague-Dawley; D016897:Respiratory Burst / Q000187:drug effects
D000975:Antioxidants; D005419:Flavonoids; D010545:Peroxides; C049375:perhydroxyl radical; D009240:N-Formylmethionine Leucyl-Phenylalanine; D000244:Adenosine Diphosphate; C068573:IdB 1031; D002251:Carbon Tetrachloride; D007501:Iron; D011493:Protein Kinase C