Abstract
Pro-oxidant effects of phenolic compounds are usually correlated to the one-electron redox potential of the phenoxyl radicals. Here we demonstrated that, besides their oxidizability, hydrophobicity can also be a decisive factor. We found that esterification of protocatechuic acid (P0) provoked a profound influence in its pro-oxidant capacity. The esters bearing alkyl chains containing two (P2), four (P4) and seven (P7) carbons, but not the acid precursor (P0), were able to exacerbate the oxidation of trolox, α-tocopherol and rifampicin. This effect was also dependent on the catechol moiety, since neither gallic acid nor butyl gallate showed any pro-oxidant effects. A comparison was also made with apocynin, which is well-characterized regarding its pro-oxidant properties. P7 was more efficient than apocynin regarding co-oxidation of trolox. However, P7 was not able to co-oxidize glutathione and NADH, which are targets of the apocynin radical. A correlation was found between pro-oxidant capacity and the stability of the radicals, as suggested by the intensity of the peak current in the differential pulse voltammetry experiments. In conclusion, taking into account that hydroquinone and related moieties are frequently found in biomolecules and quinone-based chemotherapeutics, our demonstration that esters of protocatechuic acid are specific and potent co-catalysts in their oxidations may be very relevant as a pathway to exacerbate redox cycling reactions, which are usually involved in their biological and pharmacological mechanisms of action.
Highlights
A pro-oxidant effect is a general term used when biological, chemical or physical events are able to initiate or exacerbate, by different mechanisms, a redox imbalance
Chemicals Protocatechuic acid, ethyl protocatechuate, gallic acid, butyl gallate, 3,5-dihydroxybenzoic acid, apocynin, trolox, a-tocopherol, glutathione (GSH), rifampicin, horseradish peroxidase (HRP), reduced nicotinamide adenine dinucleotide (NADH), diethylenetriaminepentaacetic acid (DTPA), 2,29-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS), catalase, 5,59-dithiobis(2-nitrobenzoic acid) (DTNB) and N,N9-dicyclohexylcarbodiimide were purchased from Sigma-Aldrich Chemical Co
It must be emphasized that for phenolic and other redox active compounds, the distinction between antiand pro-oxidant effects might be related to the stability and reactivity of the transient phenoxyl radicals generated during their oxidation
Summary
A pro-oxidant effect is a general term used when biological, chemical or physical events are able to initiate or exacerbate, by different mechanisms, a redox imbalance. It can be directly or indirectly related to the generation of reactive oxygen species (ROS) or to the inhibition of endogenous protective antioxidant systems. There are numerous and growing evidences that compounds of natural or synthetic origin usually accepted as classical antioxidants can act as pro-oxidants. It is common that their pro-oxidant properties are involved in their beneficial biological effects This is the case with ascorbic acid and vitamin K3, which are the active components in Apatone, a drug combination that has been used to kill tumour cells. The mechanism for the pharmacological action of Apatone is linked to the redox cycling of ascorbic acid, which induces a pro-oxidant effect and provokes the death of tumour cells by autoschizis [2]
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