Quantitative structure-activity relationship of flavonoids for inhibition of heterocyclic amine mutagenicity

Abstract

The mutagenic/carcinogenic heterocyclic amines formed during the cooking of protein foods have been determined to be a potential risk to human health. Therefore, mitigation measures are beginning to be studied. A recent finding is that the induction of mutation in Salmonella by these amines can be inhibited by the addition of flavonoids to the assay. This study combines data on the inhibitory process with structural, ab initio quantum chemical, hydropathic, and antioxidant factors to develop a quantitative structure‐activity relationship (QSAR) database and statistical analysis. For 39 diverse flavonoids the inhibitory potency varied approximately 100‐fold. Three predictive variables, in order of decreasing contribution to variance, are: (1) a large dipole moment; (2) after geometric minimization of energy, a small departure from planarity (i.e., small dihedral angle between the benzopyran nucleus and the attached phenyl ring), and a low rotational energy barrier to achieving planarity; and (3) fewer hydroxyl groups on the phenyl ring. However, these variables account for less than half of the variance in inhibitory potency of the flavonoids. Frontier orbital energies and antioxidant or radical scavenging properties showed little or no relationship to potency. We conclude that interference by the flavonoids with cytochrome P450 activation of the promutagens is the probable mechanism for inhibition of mutagenesis, and suggest avenues for further research. Environ. Mol. Mutagen. 35:279–299, 2000 Published 2000 Wiley‐Liss, Inc.

Multivariate QSAR study on the antimutagenic activity of flavonoids against 3-NFA on Salmonella typhimurium TA98

“…It is interesting to observe that descriptors related to structural characteristics, usually accepted as important for the activity of flavonoids (e.g. number of OH groups in the molecules, Log P, or the dihedral angle between C and B ring) [19,20], were not selected, but some related characteristics can be encoded in the four selected descriptors.…”

Characterization and density functional theory study of the antioxidant activity of quercetin and its sugar-containing analogues

“…The low magnitude of the band gap energy indicates that the flavonoid compounds could be a highly reactive system. The different energy of E gap in flavonoid compounds is a representation of molecular planarity and a quantum electronic feature of the frontier orbital [29]. The analysis of band gap values obtained for quercetin, hyperin and rutin are in accord with the results of the frontier orbital theory.…”

Bioactive substances of plant origin in food - impact on genomics

“…They are also reported to influence the expression and the activity of cytochrome P450 (CYP) [19,104]. Antioxidant activities have shown little or no relationship to the above-mentioned antimutagenic/anticarcinogenic activities of flavonoids [34].…”