Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin <i>versus</i> <i>trans</i>-6-Styrylcoumarin
Monoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-01-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/3/928 |
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| author | Marco Mellado César González Jaime Mella Luis F. Aguilar Ismail Celik Fernanda Borges Eugenio Uriarte Giovanna Delogu Dolores Viña Maria J. Matos |
| author_facet | Marco Mellado César González Jaime Mella Luis F. Aguilar Ismail Celik Fernanda Borges Eugenio Uriarte Giovanna Delogu Dolores Viña Maria J. Matos |
| author_sort | Marco Mellado |
| collection | DOAJ |
| description | Monoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively on one of the MAO isoforms have been studied deeply, and coumarin has been described as a promising scaffold. In the current manuscript we describe a comparative study between 3-phenylcoumarin (<i>endo</i> coumarin-resveratrol-inspired hybrid) and <i>trans</i>-6-styrylcoumarin (<i>exo</i> coumarin-resveratrol-inspired hybrid). Crystallographic structures of both compounds were obtained and analyzed. 3D-QSAR models, in particular CoMFA and CoMSIA, docking simulations and molecular dynamics simulations have been performed to support and better understand the interaction of these molecules with both MAO isoforms. Both molecules proved to inhibit MAO-B, with <i>trans</i>-6-styrylcoumarin being 107 times more active than 3-phenylcoumarin, and 267 times more active than <i>trans</i>-resveratrol. |
| first_indexed | 2024-03-09T23:27:59Z |
| format | Article |
| id | doaj.art-2027809adf9e4501924181c9342d01b3 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T23:27:59Z |
| publishDate | 2022-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-2027809adf9e4501924181c9342d01b32023-11-23T17:14:46ZengMDPI AGMolecules1420-30492022-01-0127392810.3390/molecules27030928Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin <i>versus</i> <i>trans</i>-6-StyrylcoumarinMarco Mellado0César González1Jaime Mella2Luis F. Aguilar3Ismail Celik4Fernanda Borges5Eugenio Uriarte6Giovanna Delogu7Dolores Viña8Maria J. Matos9Instituto de Investigación y Postgrado, Facultad de Ciencias de la Salud, Universidad Central de Chile, Santiago 8330507, ChileDepartamento de Química, Universidad Técnica Federico Santa María, Valparaíso 2340000, ChileInstituto de Química y Bioquímica, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2340000, ChileInstituto de Química, Facultad de Ciencias, Pontificia Universidad Católica de Valparaíso, Valparaíso 2340000, ChileDepartment of Pharmaceutical Chemistry, Faculty of Pharmacy, Erciyes University, 38000 Kayseri, TurkeyCIQUP, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, PortugalDepartamento de Química Orgánica, Facultade de Farmacia, Universidade Santiago de Compostela, 15782 Santiago de Compostela, SpainDepartment of Life and Environmental Sciences, University of Cagliari, Monserrato, 09042 Cagliari, ItalyChronic Diseases Pharmacology Group, Center for Research in Molecular Medicine and Chronic Diseases (CIMUS), Universidade de Santiago de Compostela, 15782 Santiago de Compostela, SpainCIQUP, Departamento de Química e Bioquímica, Faculdade de Ciências, Universidade do Porto, 4169-007 Porto, PortugalMonoamine oxidases (MAOs) are attractive targets in drug design. The inhibition of one of the isoforms (A or B) is responsible for modulating the levels of different neurotransmitters in the central nervous system, as well as the production of reactive oxygen species. Molecules that act selectively on one of the MAO isoforms have been studied deeply, and coumarin has been described as a promising scaffold. In the current manuscript we describe a comparative study between 3-phenylcoumarin (<i>endo</i> coumarin-resveratrol-inspired hybrid) and <i>trans</i>-6-styrylcoumarin (<i>exo</i> coumarin-resveratrol-inspired hybrid). Crystallographic structures of both compounds were obtained and analyzed. 3D-QSAR models, in particular CoMFA and CoMSIA, docking simulations and molecular dynamics simulations have been performed to support and better understand the interaction of these molecules with both MAO isoforms. Both molecules proved to inhibit MAO-B, with <i>trans</i>-6-styrylcoumarin being 107 times more active than 3-phenylcoumarin, and 267 times more active than <i>trans</i>-resveratrol.https://www.mdpi.com/1420-3049/27/3/9283-phenylcoumarin<i>trans</i>-6-styrylcoumarin<i>trans</i>-resveratrolmonoamine oxidase B inhibitors3D-QSAR modelsmolecular docking |
| spellingShingle | Marco Mellado César González Jaime Mella Luis F. Aguilar Ismail Celik Fernanda Borges Eugenio Uriarte Giovanna Delogu Dolores Viña Maria J. Matos Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin <i>versus</i> <i>trans</i>-6-Styrylcoumarin Molecules 3-phenylcoumarin <i>trans</i>-6-styrylcoumarin <i>trans</i>-resveratrol monoamine oxidase B inhibitors 3D-QSAR models molecular docking |
| title | Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin <i>versus</i> <i>trans</i>-6-Styrylcoumarin |
| title_full | Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin <i>versus</i> <i>trans</i>-6-Styrylcoumarin |
| title_fullStr | Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin <i>versus</i> <i>trans</i>-6-Styrylcoumarin |
| title_full_unstemmed | Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin <i>versus</i> <i>trans</i>-6-Styrylcoumarin |
| title_short | Coumarin-Resveratrol-Inspired Hybrids as Monoamine Oxidase B Inhibitors: 3-Phenylcoumarin <i>versus</i> <i>trans</i>-6-Styrylcoumarin |
| title_sort | coumarin resveratrol inspired hybrids as monoamine oxidase b inhibitors 3 phenylcoumarin i versus i i trans i 6 styrylcoumarin |
| topic | 3-phenylcoumarin <i>trans</i>-6-styrylcoumarin <i>trans</i>-resveratrol monoamine oxidase B inhibitors 3D-QSAR models molecular docking |
| url | https://www.mdpi.com/1420-3049/27/3/928 |
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