Mutagenicities of 61 flavonoids and 11 related compounds.

The mutagenicities of 61 flavonoids (naturally occurring flavonoid aglycones and flavonal glycosides and synthetic flavonoids) and those of 11 compounds structurally related to flavonoids were tested with Salmonella typhimurium strains TA100 and TA98. Among the 22 flavone derivatives tested, only wogonin was strongly mutagenic, while five derivatives, apigenin triacetate, acacetin, chrysoeriol, pedalitin, and pedalitin tetraacetate, were only weakly mutagenic. Two bisflavonyl derivatives, neither of which has a 3-hydroxyl group, were not mutagenic. Of the 16 flavonol derivatives tested, all except 3-hydroxyflavone and the tetra- and penta-methyl ethers of quercetin were mutagenic. Of the five flavanone derivatives tested, only 7,4-dihydroxyflavanone was mutagenic, showing weak activity. Of the four flavanolol derivatives tested, hydrorobinetin and taxifolin were weakly mutagenic. Of the six isoflavone derivatives tested, tectorigenin was weakly mutagenic. Of the 11 compounds in the miscellaneous group structurally related to flavonoids, only isoliquiritigenin was mutagenic, showing weak activity. For the emergence of strong mutagenicity, the double bond between positions 2 and 3 and the hydroxyl group at position 3 are required, except in wogonin, which does not have a hydroxyl group at position 3 but is strongly mutagenic to TA100. The 3-O-acetyl ester of flavonol, quercetin, was mutagenic with S9 mix, but 3-O-methyl ethers were not. Six flavonol glycosides, three quercetin glycosides and three kaempferol glycosides were mutagenic after preincubation with "hesperidinase," a crude extract of Aspergillus niger. Of 66 flavonoid agylcones and compounds structurally related to flavonoids, quercetin was the strongest mutagen. The carcinogenicity of this compound should be clarified because it is ubiquitously found in vegetables.