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Prezzavento, O; Arena, E; Parenti, C; Pasquinucci, L; Aricò, G; Scoto, G. M; Grancara, S; Toninello, A; Ronsisvalle, S
Journal of medicinal chemistry, 03/2013, Letnik: 56, Številka: 6Journal Article
Herein we report the synthesis of new bifunctional sigma-1 (σ1)-selective ligands with antioxidant activity. To achieve this goal, we combined the structure of lipoic acid, a universal antioxidant, with an appropriate sigma aminic moiety. Ligands 14 and 26 displayed high affinity and selectivity for σ1 receptors (K iσ1 = 1.8 and 5.5 nM; K iσ2/σ1 = 354 and 414, respectively). Compound 26 exhibited in vivo antiopioid effects on kappa opioid (KOP) receptor-mediated analgesia. In rat liver and brain mitochondria (RLM, RBM), this compound significantly reduced the swelling and the oxidation of thiol groups induced by calcium ions. Our results demonstrate that the tested compound has protective effects against oxidative stress.
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JCR | SNIP | JCR | SNIP | JCR | SNIP | JCR | SNIP |
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