Amidinoquinoxaline-Based Nitrones as Lipophilic Antioxidants
Nadia Gruber,
Liliana Orelli,
Cristina Minnelli,
Luca Mangano,
Emiliano Laudadio,
Giovanna Mobbili,
Pierluigi Stipa
Affiliations
Nadia Gruber
Química Ogánica II, Departamento de Ciencias Químicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Junín 956, Buenos Aires 1113, Argentina
Liliana Orelli
Química Ogánica II, Departamento de Ciencias Químicas, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, CONICET, Junín 956, Buenos Aires 1113, Argentina
Cristina Minnelli
Dipartimento di Scienze della Vita e dell’Ambiente (DISVA), Università Politecnica delle Marche, via Brecce Bianche, 60131 Ancona, Italy
Luca Mangano
F. Hoffmann-La Roche AG, Grenzacherstrasse 124, 4070 Basel, Switzerland
Emiliano Laudadio
Dipartimento di Scienze e Ingegneria della Materia, dell’Ambiente ed Urbanistica (SIMAU), Università Politecnica delle Marche, via Brecce Bianche, 60131 Ancona, Italy
Giovanna Mobbili
Dipartimento di Scienze della Vita e dell’Ambiente (DISVA), Università Politecnica delle Marche, via Brecce Bianche, 60131 Ancona, Italy
Pierluigi Stipa
Dipartimento di Scienze e Ingegneria della Materia, dell’Ambiente ed Urbanistica (SIMAU), Università Politecnica delle Marche, via Brecce Bianche, 60131 Ancona, Italy
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.
