Estela Guardado Yordi

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

The research and characterization of new bioactive substances, for the new design of functional foods, nutraceuticals, or drugs, has been intensified. Several studies showing controversial results of exogenous antioxidants, debating that the type, dosage and matrix of these antioxidants may be determining factors impacting the balance between beneficial and deleterious effects of these natural compounds (Bouayed & Bohn, 2010). There are also some proofs that they act as pro-oxidants, under certain conditions, such as high doses or the presence of metal ions (Decker, 1997; Raza & John, 2005; Watjen et al., 2005). The antioxidant or pro-oxidant activity intimately depends on their concentration (Bouayed & Bohn, 2010). The consequences of pro-oxidant activity could be the possible damage to the biomolecules such as DNA, proteins and lipids, and the consequent cellular death (Aruoma, 2003).

Structural alerts for predicting clastogenic activity of pro-oxidant flavonoid compounds: quantitative structure-activity relationship study.

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.

In silico study of new structural alerts of agents clastogenic

Natural polyphenols and their derivatives from diet have been reported by their pro-oxidant and clastogenic activities. In an aim of elucidating structural alerts for this genotoxicity endpoint, a QSTR study was conducted under the TOPS-MODE approach. It was possible to establish structural alerts from the DNA oxidative damage as an endpoint of clastogenicity at optimum leaders with high probability of being clastogenic. Some important fragments to obviate this activity were also identified. The results constitute a reference system for designing new food or pharmaceutical matrices as an alternative to the experimental toxicology.