Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage
Antonio D’Errico,
Rosarita Nasso,
Rosario Rullo,
Jessica Maiuolo,
Paola Costanzo,
Sonia Bonacci,
Manuela Oliverio,
Emmanuele De Vendittis,
Mariorosario Masullo,
Rosaria Arcone
Affiliations
Antonio D’Errico
Department of Medical, Movement and Well-Being Sciences, University of Naples “Parthenope”, Via Medina, 40, 80133 Napoli, Italy
Rosarita Nasso
Department of Medical, Movement and Well-Being Sciences, University of Naples “Parthenope”, Via Medina, 40, 80133 Napoli, Italy
Rosario Rullo
Institute for the Animal Production Systems in the Mediterranean Environment, Consiglio Nazionale delle Ricerche Piazzale Enrico Fermi 1, 80055 Portici, Italy
Jessica Maiuolo
Department of Health Science, Institute of Research for Food Safety & Health (IRC-FSH), University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
Paola Costanzo
Department of Chemistry and Chemical Technologies, University of Calabria, Via P. Bucci, Cubo 12C, 87036 Rende, Italy
Sonia Bonacci
Department of Health Sciences, University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
Manuela Oliverio
Department of Health Sciences, University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, Italy
Emmanuele De Vendittis
Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Napoli, Italy
Mariorosario Masullo
Department of Medical, Movement and Well-Being Sciences, University of Naples “Parthenope”, Via Medina, 40, 80133 Napoli, Italy
Rosaria Arcone
Department of Medical, Movement and Well-Being Sciences, University of Naples “Parthenope”, Via Medina, 40, 80133 Napoli, Italy
Monoamine oxidase and xanthine oxidase inhibitors represent useful multi-target drugs for the prevention, attenuation, and treatment of oxidative damage and neurodegenerative disorders. Chimeric molecules, constituted by naturally derived compounds linked to drugs, represent lead compounds to be explored for the discovery of new synthetic drugs acting as enzyme inhibitors. We have previously reported that seven hydroxytyrosol-donepezil hybrid compounds play a protective role in an in vitro neuronal cell model of Alzheimer’s disease. In this work, we analyzed the effects exerted by the hybrid compounds on the activity of monoamine oxidase A (MAO-A) and B (MAO-B), as well as on xanthine oxidase (XO), enzymes involved in both neurodegenerative disorders and oxidative stress. The results pointed to the identification, among the compounds tested, of selective inhibitors between the two classes of enzymes. While the 4-hydroxy-3-methoxyphenethyl 1-benzylpiperidine-4-carboxylate- (HT3) and the 4-hydroxyphenethyl 1-benzylpiperidine-4-carboxylate- donepezil derivatives (HT4) represented the best inhibitors of MAO-A, with a scarce effect on MAO-B, they were almost ineffective on XO. On the other hand, the 4,5-dihydroxy-2-nitrophenethyl 1-benzylpiperidine-4-carboxylate donepezil derivative (HT2), the least efficient MAO inhibitor, acted like the best XO inhibitor. Therefore, the differential enzymatic targets identified among the hybrid compounds synthesized enhance the possible applications of these polyphenol-donepezil hybrids in neurodegenerative disorders and oxidative stress.
