Synthesis and Antioxidant Properties of HeteroBisNitrones Derived from Benzene Dicarbaldehydes
Daniel Diez-Iriepa,
Isabel Iriepa,
Francisco López-Muñoz,
José Marco-Contelles,
Dimitra Hadjipavlou-Litina
Affiliations
Daniel Diez-Iriepa
Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain
Isabel Iriepa
Departamento de Química Orgánica y Química Inorgánica, Universidad de Alcalá, Ctra. Madrid-Barcelona km 33.6, Alcalá de Henares, 28871 Madrid, Spain
Francisco López-Muñoz
Faculty of Health, Camilo José Cela University of Madrid (UCJC), 28692 Madrid, Spain
José Marco-Contelles
Laboratory of Medicinal Chemistry, Institute of Organic Chemistry (CSIC), Juan de la Cierva 3, 28006 Madrid, Spain
Dimitra Hadjipavlou-Litina
Department of Pharmaceutical Chemistry, School of Pharmacy, Faculty of Health Sciences, Aristotle University of Thessaloniki, 54124 Thessaloniki, Greece
We report herein the synthesis and antioxidant profile of nine novel heterobisnitrones (hBNs) as new α-phenyl-tert-butylnitrone (PBN) analogues. The synthesized hBNs 1–9 were evaluated for their antioxidant activity using different in vitro techniques, while they were also tested as inhibitors of soybean LOX, as an indication of their anti-inflammatory effect. Nitrone hBN9 is the most potent antioxidant presenting higher anti-lipid peroxidation and hydroxyl radicals scavenging activities as well as higher lipoxygenase inhibition. In silico calculations reveal that hBN9 follows Lipinski’s rule of five and that the molecule is able to penetrate theoretically the brain. All these results led us to propose hBN9 as a new potent antioxidant nitrone.