Synthesis of Selenium-Based Small Molecules Inspired by CNS-Targeting Psychotropic Drugs and Mediators
Due to its endogenously high oxygen consumption, the central nervous system (CNS) is vulnerable to oxidative stress conditions. Notably, the activity of several CNS-targeting compounds, such as antidepressant and hypnotic drugs, or endogenous mediators, such as melatonin, is indeed linked to their a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-06-01
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| Series: | Chemistry |
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| Online Access: | https://www.mdpi.com/2624-8549/5/3/101 |
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| author | Giovanni Ribaudo Davide Zeppilli Alberto Ongaro Marco Bortoli Giuseppe Zagotto Laura Orian |
| author_facet | Giovanni Ribaudo Davide Zeppilli Alberto Ongaro Marco Bortoli Giuseppe Zagotto Laura Orian |
| author_sort | Giovanni Ribaudo |
| collection | DOAJ |
| description | Due to its endogenously high oxygen consumption, the central nervous system (CNS) is vulnerable to oxidative stress conditions. Notably, the activity of several CNS-targeting compounds, such as antidepressant and hypnotic drugs, or endogenous mediators, such as melatonin, is indeed linked to their ability of mitigating oxidative stress. In this work, we report the synthesis of two organoselenium compounds of which the structure was inspired by CNS-targeting psychotropic drugs (zolpidem and fluoxetine) and an endogenous mediator (melatonin). The molecules were designed with the aim of combining the ROS-scavenging properties, which were already assessed for the parent compounds, with a secondary antioxidant action, a glutathione peroxidase (GPx) mimic role empowered by the presence of selenium. The compounds were obtained through a facile three-step synthesis and were predicted by computational tools to passively permeate through the blood–brain barrier and to efficiently bind to the GABA A receptor, the macromolecular target of zolpidem. Of note, the designed synthetic pathway enables the production of several other derivatives through minor modifications of the scheme, paving the way for structure–activity relationship studies. |
| first_indexed | 2024-03-10T22:55:14Z |
| format | Article |
| id | doaj.art-5d40696b3d9940f8beb41a2c1ac5989c |
| institution | Directory Open Access Journal |
| issn | 2624-8549 |
| language | English |
| last_indexed | 2024-03-10T22:55:14Z |
| publishDate | 2023-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Chemistry |
| spelling | doaj.art-5d40696b3d9940f8beb41a2c1ac5989c2023-11-19T10:01:13ZengMDPI AGChemistry2624-85492023-06-01531488149610.3390/chemistry5030101Synthesis of Selenium-Based Small Molecules Inspired by CNS-Targeting Psychotropic Drugs and MediatorsGiovanni Ribaudo0Davide Zeppilli1Alberto Ongaro2Marco Bortoli3Giuseppe Zagotto4Laura Orian5Dipartimento di Medicina Molecolare e Traslazionale, Università degli Studi di Brescia, Viale Europa 11, 25123 Brescia, ItalyDipartimento di Scienze Chimiche, Università degli Studi di Padova, Via Marzolo 1, 35131 Padova, ItalyDipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, ItalyDepartment of Chemistry and Hylleraas Centre for Quantum Molecular Sciences, University of Oslo, 0315 Oslo, NorwayDipartimento di Scienze del Farmaco, Università degli Studi di Padova, Via Marzolo 5, 35131 Padova, ItalyDipartimento di Scienze Chimiche, Università degli Studi di Padova, Via Marzolo 1, 35131 Padova, ItalyDue to its endogenously high oxygen consumption, the central nervous system (CNS) is vulnerable to oxidative stress conditions. Notably, the activity of several CNS-targeting compounds, such as antidepressant and hypnotic drugs, or endogenous mediators, such as melatonin, is indeed linked to their ability of mitigating oxidative stress. In this work, we report the synthesis of two organoselenium compounds of which the structure was inspired by CNS-targeting psychotropic drugs (zolpidem and fluoxetine) and an endogenous mediator (melatonin). The molecules were designed with the aim of combining the ROS-scavenging properties, which were already assessed for the parent compounds, with a secondary antioxidant action, a glutathione peroxidase (GPx) mimic role empowered by the presence of selenium. The compounds were obtained through a facile three-step synthesis and were predicted by computational tools to passively permeate through the blood–brain barrier and to efficiently bind to the GABA A receptor, the macromolecular target of zolpidem. Of note, the designed synthetic pathway enables the production of several other derivatives through minor modifications of the scheme, paving the way for structure–activity relationship studies.https://www.mdpi.com/2624-8549/5/3/101antioxidantCNSglutathione peroxidasemelatoninseleniumzolpidem |
| spellingShingle | Giovanni Ribaudo Davide Zeppilli Alberto Ongaro Marco Bortoli Giuseppe Zagotto Laura Orian Synthesis of Selenium-Based Small Molecules Inspired by CNS-Targeting Psychotropic Drugs and Mediators Chemistry antioxidant CNS glutathione peroxidase melatonin selenium zolpidem |
| title | Synthesis of Selenium-Based Small Molecules Inspired by CNS-Targeting Psychotropic Drugs and Mediators |
| title_full | Synthesis of Selenium-Based Small Molecules Inspired by CNS-Targeting Psychotropic Drugs and Mediators |
| title_fullStr | Synthesis of Selenium-Based Small Molecules Inspired by CNS-Targeting Psychotropic Drugs and Mediators |
| title_full_unstemmed | Synthesis of Selenium-Based Small Molecules Inspired by CNS-Targeting Psychotropic Drugs and Mediators |
| title_short | Synthesis of Selenium-Based Small Molecules Inspired by CNS-Targeting Psychotropic Drugs and Mediators |
| title_sort | synthesis of selenium based small molecules inspired by cns targeting psychotropic drugs and mediators |
| topic | antioxidant CNS glutathione peroxidase melatonin selenium zolpidem |
| url | https://www.mdpi.com/2624-8549/5/3/101 |
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