Fluoxetine scaffold to design tandem molecular antioxidants and green catalysts
Ribaudo, Giovanni 1Bortoli, Marco 2Ongaro, Alberto 1Oselladore, Erika 3Gianoncelli, Alessandra 1Zagotto, Giuseppe 3Orian, Laura2
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作者信息
1. Univ Brescia, Dipartimento Med Mol & Traslaz, Viale Europa 11, I-25123 Brescia, Italy
2. Univ Padua, Dipartimento Sci Chim, Via Marzolo 1, I-35131 Padua, Italy
3. Univ Padua, Dipartimento Sci Farmaco, Via Marzolo 5, I-35131 Padua, Italy
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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 H2O2 in 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 a trans-selective manner. This mechanism is likely to be extended to other substrates for the preparation of unsaturated cinnamylamines.
NSTL
Royal Soc Chemistry