ANTIMUTAGENIC EFFECTS OF FLAVONOIDS, CHALCONES AND STRUCTURALLY RELATED-COMPOUNDS ON THE ACTIVITY OF 2-AMINO-3-METHYLIMIDAZO[4,5-F]QUINOLINE (IQ) AND OTHER HETEROCYCLIC AMINE MUTAGENS FROM COOKED FOOD

Sixty-four flavonoids were tested for their antimutagenic potencies wi th respect to IQ in Salmonella typhimurium TA98 and in part also towar ds MeIQ, MeIQx, Trp-P-2, and Glu-P-1 and in S. typhimurium TA100. Anti mutagenic potencies were quantified by the inhibitory dose for 50% red uction of mutagenic activity (ID50). A carbonyl function at C-4 of the flavane nucleus seems to be essential for antimutagenicity: two flava nols and four anthocyanidines were inactive. Again, five isoflavons, e xcept biochanin A, were inactive. Within the other groups of 21 flavon es, 16 flavonols and 16 flavanones the parent compounds flavone, flavo nol, and flavanone possessed the highest antimutagenic potencies (ID50 : 4.1, 2.5, 5.5 nmoles). Increasing polarity by introduction of hydrox yl functions reduced antimutagenic potency. Reducing polarity of hydro xy flavonoids by methyl etherification, however, increased antimutagen ic potency again. 6-Hydroxy- and 2'-hydroxy substituted flavonoids wer e considerably less potent antimutagens. Of 11 flavonoid glycosides te sted all compounds except apigenin- and luteolin-7-glucoside (ID50: 74 , 115 nmoles) were inactive or only weakly antimutagenic. Rings C and A of the nucleus were not essential for antimutagenicity: chalcone and three derivatives were nearly as active as comparable flavones while antimutagenicity of benzylidenacetone was considerably reduced (ID50: 95 nmoles). Cinnamylaldehyde and cinnamoates, however, were inactive. A planar structure in the vicinity of the carbonyl group may also be i mportant for antimutagenicity. Flavanones were less potent antimutagen s than the corresponding flavones, but dihydrochalcones and 14 structu rally related saturated aromatic carbonyl compounds were inactive. Fis etin and 6-hydroxyflavone were competitive inhibitors, but luteolin wa s a mixed type inhibitor. The inhibition mechanisms of flavone, kaempf erol, morin, flavanone, and 2'-hydroxyflavanone were concentration dep endent, being competitive at low concentrations and mixed or non-compe titive (2'-hydroxyflavanone) at concentrations about the ID50 value. N o fundamental differences between the two tester strains and no clear influence of mutagen structure on antimutagenic potency could be detec ted.