The aim of the present study was to compare the effect of five structural classes of flavonoids on the viability and metabolism of a colonic adenocarcinoma cell line (HT29 cells). The most prominent structural features of flavonoids favoring both their cytotoxic activity and their capacity to inhibit lactate release appear to be the desaturation of the 2, 3 bond and the position of attachment of the B ring. Indeed, flavonol and flavone are the most potent and, in both classes, the order of potency can be modulated by hydroxyl or methoxyl substituents. On the other hand, in our model, we did not find any correlation between flavonoid structure and their capacity to modulate cAMP level. This last point is discussed.