Structural Alerts for Predicting Clastogenic Activity of Pro-oxidant Flavonoid Compounds: Quantitative Structure–Activity Relationship Study

Abstract

Flavonoids have been reported to exert multiple biological effects that include acting as pro-oxidants at very high doses. The authors determined a structural alert to identify the clastogenic activity of a series of flavonoids with pro-oxidant activity. The methodology was based on a quantitative structure-activity relationship (QSAR) study. Specifically, the authors developed a virtual screening method for a clastogenic model using the topological substructural molecular design (TOPS-MODE) approach. It represents a useful platform for the automatic generation of structural alerts, based on the calculation of spectral moments of molecular bond matrices appropriately weighted, taking into account the hydrophobic, electronic, and steric molecular features. Therefore, it was possible to establish the structural criteria for maximal clastogenicity of pro-oxidant flavonoids: the presence of a 3-hydroxyl group and a 4-carbonyl group in ring C, the maximal number of hydroxyl groups in ring B, the presence of methoxyl and phenyl groups, the absence of a 2,3-double bond in ring C, and the presence of 5,7 hydroxyl groups in ring A. The presented clastogenic model may be useful for screening new pro-oxidant compounds. This alert could help in the design of new and efficient flavonoids, which could be used as bioactive compounds in nutraceuticals and functional food.

Antioxidant and Pro-Oxidant Effects of Polyphenolic Compounds and Structure-Activity Relationship Evidence

“…We think it is interesting to predict, from the standpoint of polyphenolic structure-activity, the DNA damage leading to pro-oxidant substances (Yordi et al, 2011). Aruoma (2003) described that oxidative modifications to DNA are very important.…”

“…We believe that these methods can be useful for predicting a specific activity of new polyphenolic compounds and/or synthezinging polyphenols with desired properties (Yordi et al, 2011).…”

“…Readers interested in learning more about the procedure for calculating work can be found in (Estrada & Molina, 2006). Yordi et al (2011) calculated the bond contribution to the clastogenic activity of compounds with reported pro-oxidant activity. Figure 6 shows one example of the calculated bond fragment.…”

Influence of thermodynamic parameters on the genotoxicity of bioactive phenolic compounds present in food

“…There are reports of phenolic substances with clastogenic activity. It has also been predicted by in silico studies that some substances reported to have pro-oxidant activity can be clastogenic [13,14].…”

“…In order to predict the clastogenic activity of phenolic compounds with reported pro-oxidant activity, QSAR methods have been employed [13,14] and they have been interpreted, in structural terms, structure-activity relationships. This has allowed the identification of structural alerts associated with clastogenic activity using the TOPSMODE approach.…”