Browsing by Author "Pittala, Valeria"

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New Bifunctional Antioxidant/Σ1 Agonist Ligands: Preliminary Chemico-Physical and Biological Evaluation
(Pergamon-Elsevier Science Ltd, 2016) Arena, Emanuela; Cacciatore, Ivana; Cerasa, Laura S.; Turkez, Hasan; Pittala, Valeria; Pasquinucci, Lorella; Prezzavento, Orazio
We previously reported bifunctional sigma-1 (sigma(1)) ligands endowed with antioxidant activity (1 and 2). In the present paper, pure enantiomers (R)-1 and (R)-2 along with the corresponding p-methoxy (6, 11), p-fluoro derivatives (7, 12) were synthesized. sigma(1) and sigma(2) affinities, antioxidant properties, and chemico-physical profiles were evaluated. Para derivatives, while maintaining strong sigma(1) affinity, displayed improved sigma(1) selectivity compared to the parent compounds 1 and 2. In vivo evaluation of compounds 1, 2, (R)-1, 7, and 12 showed sigma(1) agonist pharmacological profile. Chemico-physical studies revealed that amides 2, 11 and 12 were more stable than corresponding esters 1, 6 and 7 under our experimental conditions. Antioxidant properties were exhibited by fluoro derivatives 7 and 12 being able to increase total antioxidant capacity (TAC). Our results underline that p-substituents have an important role on sigma(1) selectivity, TAC, chemical and enzymatic stabilities. In particular, our data suggest that new very selective compounds 7 and 12 could be promising tools to investigate the disorders in which sigma(1) receptor dysfunction and oxidative stress are contemporarily involved. (C) 2016 Elsevier Ltd. All rights reserved.