Fluoxetine finds application in the treatment of depression and mood disorders. This selective serotonin-reuptake inhibitor (SSRI) also contrasts oxidative stress by direct ROS scavenging, modulation of the endogenous antioxidant defense system, and/or enhancement of the serotonin antioxidant capacity. We synthesised some fluoxetine analogues incorporating a selenium nucleus, thus expanding its antioxidant potential by enabling a hydroperoxides-inactivating, glutathione peroxidase (GPx)-like activity. Radical scavenging and peroxidatic activity were combined in a water-soluble, drug-like, tandem antioxidant molecule. Selenofluoxetine derivatives were reacted with H2O2in water, and the mechanistic details of the reaction were unravelled combining nuclear magnetic resonance (NMR), electrospray ionisation-mass spectrometry (ESI-MS) and quantum chemistry calculations. The observed oxidation-elimination process led to the formation of seleninic acid and cinnamylamine in atrans-selective manner. This mechanism is likely to be extended to other substrates for the preparation of unsaturated cinnamylamines.

Fluoxetine scaffold to design tandem molecular antioxidants and green catalysts

Bortoli M.;Oselladore E.;Zagotto G.;Orian L.
2020

Abstract

Fluoxetine finds application in the treatment of depression and mood disorders. This selective serotonin-reuptake inhibitor (SSRI) also contrasts oxidative stress by direct ROS scavenging, modulation of the endogenous antioxidant defense system, and/or enhancement of the serotonin antioxidant capacity. We synthesised some fluoxetine analogues incorporating a selenium nucleus, thus expanding its antioxidant potential by enabling a hydroperoxides-inactivating, glutathione peroxidase (GPx)-like activity. Radical scavenging and peroxidatic activity were combined in a water-soluble, drug-like, tandem antioxidant molecule. Selenofluoxetine derivatives were reacted with H2O2in water, and the mechanistic details of the reaction were unravelled combining nuclear magnetic resonance (NMR), electrospray ionisation-mass spectrometry (ESI-MS) and quantum chemistry calculations. The observed oxidation-elimination process led to the formation of seleninic acid and cinnamylamine in atrans-selective manner. This mechanism is likely to be extended to other substrates for the preparation of unsaturated cinnamylamines.
2020
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11577/3350047
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