| Aldehyde oxidase (AO), a cytosolic molybdenum-containing hydroxylase, is predominantly active in liver
and other tissues of mammalian species and involved in the metabolism of extensive range of aldehydes
and nitrogen-containing compounds. A wide range of natural components including polyphenols are able
to interfere with AO-catalyzed reactions. Polyphenols and flavonoids are one of the extensive secondary
plant metabolites ubiquitously present in plants considered an important part of the human diet. The aim
of the present study was to investigate inhibitory effect of selected phenolic compounds from three subclasses of aurone, flavanone and phenolic lactone compounds on the activity of AO, spectrophotometrically. AO enzyme was partially purified from liver of guinea pig. Then, inhibitory effects of 10 flavonoid
compounds including 8 derivatives of 2-benzylidenebenzofuran-3(2H)-ones, as well as naringenin and
ellagic acid on the activity of aldehyde oxidase were assessed compared with the specific inhibitor of
AO, menadione. Among the phenolic compounds with inhibitory effects on the enzyme, ellagic acid
(IC50 = 14.47 lM) was the most potent agent with higher inhibitory action than menadione
(IC50 = 31.84 lM). The mechanisms by which flavonoid compounds inhibit AO activity have been also
determined. The inhibitory process of the assessed compounds occurs via either a non-competitive or
mixed mode. Although flavonoid compounds extensively present in the nature, mainly in dietary regimen, aurones with promising biological properties are not widely distributed in nature, so synthesis of
aurone derivatives is of great importance. Additionally, aurones seem to provide a promising scaffold
in medicinal chemistry for the skeleton of new developing drugs, so the results of the current study
can be valuable in order to better understanding drug–food as well as drug–drug interaction and also
appears to be worthwhile in drug development strategies. |