| Flavonoids (phenylbenzo-{dollar}gamma{dollar}-pyrone) are ubiquitous plant natural products that have diverse physiological activities. In view of the fact that dietary consumption of flavonoids in the United States is significant (approximately 1 g/day), an understanding of the metabolic profile of these natural products is of considerable interest.; In order to achieve predictability in the biotransformation of flavonoids, the following substrates were investigated: flavone, flavanone, isoflavone, isoflavanone, chromone, chromanone and three ring A hydroxyflavones. Hydroxylation reactions at 4{dollar}spprime{dollar} and 3{dollar}spprime{dollar},4{dollar}spprime{dollar} positions occurred in all substrates indicating broad substrate specificity for this hydroxylase system. On the other hand, hydroxylation at C-2 and C-3 occurred only in case of flavanone and isoflavanone. In most of the cases, no hydroxylation occurred in ring A raising the possibility that the chromone ring system is the part of the molecule which binds to the enzyme system thus exposing the C-3{dollar}spprime{dollar}, C-4{dollar}spprime{dollar}, C-2 and C-3 positions to the hydroxylating site of the enzyme.; Ring C cleavage occurred in flavone and flavanone. Two cleavage products of flavone were identified as o-hydroxyphenyl-hydroxymethyl ketone and its reduction product. All cleavage products of flavanone were found to be dihydrochalcones. Carbonyl reduction occurred only in case of flavanone giving rise to an optically active metabolite having 4{dollar}alpha{dollar} configuration. All the remaining transformations were found to be non enantioselective. Dehydrogenation of flavanone, isoflavanone and chromanone at C2-C3 was achieved by the same organism indicating broad substrate specificity for this type of reaction. A unique metabolite that was observed in the biotransformation of 5-hydroxyflavone is the sulfation product.; The binding characteristics of 20 flavonoid metabolites and substrates to estrogen receptor using estrogen-receptor competition assay was determined. Only metabolites having hydroxy group in ring A and another group at 4{dollar}spprime{dollar}-position were found to be active.; 7-Hydroxyflavone was the most potent aromatase inhibitor among the 20 compounds tested. Other compounds including flavanone, flavone, 4{dollar}spprime{dollar}-hydroxyflavanone and 7,4{dollar}spprime{dollar}-dihydroxyflavone were also found to be active. The remaining compounds showed only slight activity as aromatase inhibitors. |
