Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage
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 exp...
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| Format: | Article |
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MDPI AG
2024-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/29/2/548 |
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| author | Antonio D’Errico Rosarita Nasso Rosario Rullo Jessica Maiuolo Paola Costanzo Sonia Bonacci Manuela Oliverio Emmanuele De Vendittis Mariorosario Masullo Rosaria Arcone |
| author_facet | Antonio D’Errico Rosarita Nasso Rosario Rullo Jessica Maiuolo Paola Costanzo Sonia Bonacci Manuela Oliverio Emmanuele De Vendittis Mariorosario Masullo Rosaria Arcone |
| author_sort | Antonio D’Errico |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-08T09:48:20Z |
| format | Article |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-08T09:48:20Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-00a40ae28811490dae91c142cf6fa9542024-01-29T14:09:29ZengMDPI AGMolecules1420-30492024-01-0129254810.3390/molecules29020548Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative DamageAntonio D’Errico0Rosarita Nasso1Rosario Rullo2Jessica Maiuolo3Paola Costanzo4Sonia Bonacci5Manuela Oliverio6Emmanuele De Vendittis7Mariorosario Masullo8Rosaria Arcone9Department of Medical, Movement and Well-Being Sciences, University of Naples “Parthenope”, Via Medina, 40, 80133 Napoli, ItalyDepartment of Medical, Movement and Well-Being Sciences, University of Naples “Parthenope”, Via Medina, 40, 80133 Napoli, ItalyInstitute for the Animal Production Systems in the Mediterranean Environment, Consiglio Nazionale delle Ricerche Piazzale Enrico Fermi 1, 80055 Portici, ItalyDepartment of Health Science, Institute of Research for Food Safety & Health (IRC-FSH), University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, ItalyDepartment of Chemistry and Chemical Technologies, University of Calabria, Via P. Bucci, Cubo 12C, 87036 Rende, ItalyDepartment of Health Sciences, University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, ItalyDepartment of Health Sciences, University Magna Græcia of Catanzaro, Viale Europa, 88100 Catanzaro, ItalyDepartment of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Via S. Pansini 5, 80131 Napoli, ItalyDepartment of Medical, Movement and Well-Being Sciences, University of Naples “Parthenope”, Via Medina, 40, 80133 Napoli, ItalyDepartment of Medical, Movement and Well-Being Sciences, University of Naples “Parthenope”, Via Medina, 40, 80133 Napoli, ItalyMonoamine 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.https://www.mdpi.com/1420-3049/29/2/548hydroxytyrosol-donepezil hybridinflammatory diseasesneurodegenerative disordersmonoamine oxidase (MAO)xanthine oxidase (XO)multitargeting agents |
| spellingShingle | Antonio D’Errico Rosarita Nasso Rosario Rullo Jessica Maiuolo Paola Costanzo Sonia Bonacci Manuela Oliverio Emmanuele De Vendittis Mariorosario Masullo Rosaria Arcone Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage Molecules hydroxytyrosol-donepezil hybrid inflammatory diseases neurodegenerative disorders monoamine oxidase (MAO) xanthine oxidase (XO) multitargeting agents |
| title | Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage |
| title_full | Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage |
| title_fullStr | Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage |
| title_full_unstemmed | Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage |
| title_short | Effect of Hydroxytyrosol Derivatives of Donepezil on the Activity of Enzymes Involved in Neurodegenerative Diseases and Oxidative Damage |
| title_sort | effect of hydroxytyrosol derivatives of donepezil on the activity of enzymes involved in neurodegenerative diseases and oxidative damage |
| topic | hydroxytyrosol-donepezil hybrid inflammatory diseases neurodegenerative disorders monoamine oxidase (MAO) xanthine oxidase (XO) multitargeting agents |
| url | https://www.mdpi.com/1420-3049/29/2/548 |
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