Mutagenicities of 61 flavonoids and 11 related compounds

Abstract

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.

Detoxification of Genotoxic Compounds as a Threshold Mechanism Limiting Their Carcinogenicity

“…Other compounds eliciting direct damage in E. coli DNA, which is eliminated in the presence of liver homogenates, are aniline and its urinary metabolites o-and p-aminophenol, the carcinogenic properties of which are still under discussion (12). A compound of special interest is the flavonoid quercitin, the only genotoxic agent exhibiting sharply contrasting metabolic trends in bacterial systems (increase of activity in the reversion test and complete deactivation in the DNA-repair test), as well as conflicting effects in animal carcinogenicity tests (13).…”

Mutagenicidade e estrogenicidade de plantas da família Eriocaulaceae e relação estrutura-atividade de algumas substâncias isoladas

“…A structure-activity relationship of certain flavonoids, which exhibit positive mutagenicity in the S. typhimurium reversion assay, was identified in some earlier studies (16)(17)(18)(19)(20).…”

“…The flavonoid (4) possesses a sugar at position 3 on C the ring and its mutagenicity was considered negative in the absence of metabolization. With S9 metabolization, probably this sugar was also removed and the hydroxyl group restored, favoring the appearance of the mutagenicity (17,19).…”

“…Além de um crescente interesse na avaliação da mutagenicidade de muitos flavonóides conhecidos, através do teste de Ames, alguns pesquisadores estabeleceram a relação estruturaatividade de certos flavonóides que apresentaram mutagenicidade positiva no teste de reversão com Salmonella typhimurium EDENHARDER et al, 1993;MACGREGOR e JURD, 1978;NAGAO et al, 1981e SANDNESS et al, 1992.…”

“…The establishment of the structure-activity relationship of certain flavonoids and naphthopyranones, in the S. typhimurium reversion assay, has made a great contribution to the improved understanding of the possible effects and mechanisms of action of those compounds and is very useful in making comparisons between similar compounds obtained from different species of plant (8)(9)(10)(16)(17)(18)(19)(20) The aim of this report was to determine the mutagenic effect of enriched fractions and substances isolated from E. ligulatum (Vell.) L.B.…”