Amidinoquinoxaline-Based Nitrones as Lipophilic Antioxidants

The potential of nitrones (N-oxides) as therapeutic antioxidants is due to their ability to counteract oxidative stress, mainly attributed to their action as radical scavengers toward C- and O-centered radicals. Among them, nitrones from the amidinoquinoxaline series resulted in interesting derivatives, due to the ease with which it is possible to introduce proper substituents within their structure in order to modulate their lipophilicity. The goal is to obtain lipophilic antioxidants that are able to interact with cell membranes and, at the same time, enough hydrophilic to neutralize those radicals present in a water compartment. In this work, the antioxidant efficacy of a series of amidinoquinoxaline nitrones has been evaluated regarding the oxidation of 2-deoxyribose and lipid peroxidation. The results have been rationalized on the basis of the different possible mechanisms involved, depending on some of their properties, such as lipophilicity, the ability to scavenge free radicals, and to undergo single electron transfer (SET) reactions.

Automated summary

Nitrones have potential as therapeutic antioxidants by scavenging C- and O-centered radicals, with the ability to modulate their structure by introducing proper substituents to interact with cell membranes and neutralize radicals in water compartments. The antioxidant efficacy of amidinoquinoxaline nitrones is based on properties such as lipophilicity, free radical scavenging ability, and single electron transfer reactions.