Abstract A38: Structure-activity relationship of closely-related flavonoids with possible chemopreventive qualities Free

A38

Dietary flavonoids are now widely presumed to have human health benefits, and increased intake is epidemiologically correlated with decreased risk of cardiovascular disease and cancer. The general mechanisms thought to be involved in chemoprevention through dietary compounds include the inhibition of the carcinogen-bioactivating phase I enzymes and/or induction of carcinogen-bioinactivating phase II enzymes. Methoxylated flavonoids have been shown to have chemopreventive activity in a number of in vitro assays, and we have selected 27 of them as the objects of this work. Furthermore, these flavonoids were analyzed to investigate possible structure-activity relationships for effective, non-toxic agents with chemopreventive potential.

The flavonoids are a structurally diverse class of low molecular weight polyphenolic benzo-c-pyrone derivatives. The basic structure is composed of two benzene rings (A and B) separated by an oxygen-containing heterocyclic ring. Substituent groups can attach on each of the molecule’s rings, with hydroxyl, methoxy groups or sugar moieties being present most frequently. Neither hydroxylation nor methoxylation solely on the B-ring had a strong inducing effect on the phase II enzyme NAD(P)H:quinone-reductase (NQO1) in murine hepatoma cells. However, flavonoids with a methoxy-group substitution at the 5-position of the A-ring were the most potent inducers of NQO1. Other flavonoids were equally potent inducers, but exhibited much higher toxicity in at least one of the cell lines tested. Certain methoxylated flavonoids that are found in dietary fruits and vegetables have significant potential for prevention of chemically-induced carcinogenesis and should be investigated further in animal models of cancer prevention.

Citation Information: Cancer Prev Res 2008;1(7 Suppl):A38.