6533b7d9fe1ef96bd126ca91

RESEARCH PRODUCT

Structure-Activity Relations of Flavonoids as Antimutagens Against Cooked Food Mutagens and Nitroarenes in the Salmonella Reversion Assay

subject

description

When about 60 flavonoids were tested for their antimutagenic potencies against 2-amino-3-methylimidazo [4,5-f]quinoline (IQ) and the nitroarenes 2-nitrofluorene (2-NF), 1-nitropyrene (1-NP), and 3-nitrofluoranthene (3-NFA) in the Salmonella reversion assay, distinct structure-activity relations were detected. With both groups of compounds, flavonoid glycosides were inactive or at best weakly active. Catechins and anthocyanidins, which lack the carbonyl function at C-4 of the flavane nucleus, were inactive. In contrast, chalcones exerted strong antimutagenicity against IQ and the nitroarenes. With respect to IQ, flavonoids of low polarity were the most active compounds: The parent compounds flavone, flavanone, and flavonol possessed the highest antimutagenic potencies. Increasing polarity by introduction of hydroxyl groups reduced antimutagenic potency, and reducing polarity by methyl etherification of hydroxyl functions increased antimutagenic potency again. Positive correlations were found between the polarity of flavonoids and antimutagenic potency concerning nitroarenes, though an optimum number of hydroxyl functions existed with respect to antimutagenicity. In general, the tetracyclic nitroarenes 1-NP and 3-NFA were more effectively antagonized than the tricyclic 2-NF. Flavonoids inhibited the activation of IQ by rat liver cytochrome P-450-dependent monooxygenases, as indicated by inhibition of 7-methoxy- and 7-ethoxyresorufindealkylases. Again, mutagenicity of N-hydroxy-IQ (phase II reactions) was reduced by flavonoids—best by some polar flavonoids (e.g., luteolin).