Structural characteristics that determine the inhibitory role of phenolic compounds on 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formation

• PhIP formation is mainly inhibited by m-dihydroxybenzenes.
• PhIP formation is poorly inhibited by o- and p-dihydroxybenzenes.
• o- and p-dihydroxybenzenes promote PhIP formation at low phenol concentration.
• The effect of complex phenols is the combination of the effects of their phenolic components.
• o-, m-, and p-dihydroxybenzenes inhibit degradation of phenylalanine.

In an attempt to understand the structural characteristics of phenolic compounds that favour the inhibition of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) formation, this study analyzes the role of twenty-five phenolic compounds on the PhIP produced in phenylalanine/creatinine/oxidised lipid reaction mixtures. The results showed that phenols having two hydroxy groups at meta positions of the aromatic ring were the most efficient inhibitors. The presence of alkyl or carboxylic groups as additional substituents in the aromatic ring slightly reduced the inhibitory effect. On the other hand, the introduction of additional hydroxy and amino groups mostly cancelled the inhibitory effect, which was also mostly absent in ortho and para dihydroxy derivatives. In complex phenols, the presence of several rings with opposite effects produced a reduced inhibitory effect. All these results suggest that it is possible to predict if a phenolic derivative will inhibit the formation of PhIP, or not, based on its structure.