Design, Synthesis, and In Vivo and In Silico Evaluation of Coumarin Derivatives with Potential Antidepressant Effects
In this study, a series of coumarin derivatives were designed and synthesized, their structures were characterized using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) testing methods. In the pharmacological experiment, two behavior-monitoring methods, the forced swim...
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| Format: | Article |
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MDPI AG
2021-09-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/18/5556 |
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| author | Xuekun Wang Hao Zhou Xinyu Wang Kang Lei Shiben Wang |
| author_facet | Xuekun Wang Hao Zhou Xinyu Wang Kang Lei Shiben Wang |
| author_sort | Xuekun Wang |
| collection | DOAJ |
| description | In this study, a series of coumarin derivatives were designed and synthesized, their structures were characterized using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) testing methods. In the pharmacological experiment, two behavior-monitoring methods, the forced swim test (FST) and the tail suspension test (TST), were used to determine the antidepressant activity of coumarin derivatives. Compounds that showed potential activity were analyzed for their effects on 5-hydroxytryptamine (5-HT) levels in the brains of mice. Molecular docking experiments to simulate the possible interaction of these compounds with the 5-HT<sub>1A</sub> receptor was also be predicted. The results of the pharmacological experiments showed that most coumarin derivatives exhibited significant antidepressant activity. Among these compounds, 7-(2-(4-(4-fluorobenzyl)piperazin-1-yl)-2-oxoethoxy)-2<i>H</i>-chromen-2-one (6i) showed the highest antidepressant activity. The results of the measurement of 5-HT levels in the brains of mice indicate that the antidepressant activity of coumarin derivatives may be mediated by elevated 5-HT levels. The results of molecular docking demonstrated that compound 6i had a significant interaction with amino acids around the active site of the 5-HT<sub>1A</sub> receptor in the homology model. The physicochemical and pharmacokinetic properties of the target compounds were also predicted using Discovery Studio (DS) 2020 and Chemdraw 14.0. |
| first_indexed | 2024-03-10T07:24:03Z |
| format | Article |
| id | doaj.art-50db837922b7448bb9b337d40a816dc6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T07:24:03Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-50db837922b7448bb9b337d40a816dc62023-11-22T14:24:55ZengMDPI AGMolecules1420-30492021-09-012618555610.3390/molecules26185556Design, Synthesis, and In Vivo and In Silico Evaluation of Coumarin Derivatives with Potential Antidepressant EffectsXuekun Wang0Hao Zhou1Xinyu Wang2Kang Lei3Shiben Wang4School of Pharmaceutical Sciences, Liaocheng University, Liaocheng 252059, ChinaSchool of Pharmaceutical Sciences, Liaocheng University, Liaocheng 252059, ChinaSchool of Pharmaceutical Sciences, Liaocheng University, Liaocheng 252059, ChinaSchool of Pharmaceutical Sciences, Liaocheng University, Liaocheng 252059, ChinaSchool of Pharmaceutical Sciences, Liaocheng University, Liaocheng 252059, ChinaIn this study, a series of coumarin derivatives were designed and synthesized, their structures were characterized using nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS) testing methods. In the pharmacological experiment, two behavior-monitoring methods, the forced swim test (FST) and the tail suspension test (TST), were used to determine the antidepressant activity of coumarin derivatives. Compounds that showed potential activity were analyzed for their effects on 5-hydroxytryptamine (5-HT) levels in the brains of mice. Molecular docking experiments to simulate the possible interaction of these compounds with the 5-HT<sub>1A</sub> receptor was also be predicted. The results of the pharmacological experiments showed that most coumarin derivatives exhibited significant antidepressant activity. Among these compounds, 7-(2-(4-(4-fluorobenzyl)piperazin-1-yl)-2-oxoethoxy)-2<i>H</i>-chromen-2-one (6i) showed the highest antidepressant activity. The results of the measurement of 5-HT levels in the brains of mice indicate that the antidepressant activity of coumarin derivatives may be mediated by elevated 5-HT levels. The results of molecular docking demonstrated that compound 6i had a significant interaction with amino acids around the active site of the 5-HT<sub>1A</sub> receptor in the homology model. The physicochemical and pharmacokinetic properties of the target compounds were also predicted using Discovery Studio (DS) 2020 and Chemdraw 14.0.https://www.mdpi.com/1420-3049/26/18/5556coumarinsynthesisantidepressantFST5-HTmolecular docking studies |
| spellingShingle | Xuekun Wang Hao Zhou Xinyu Wang Kang Lei Shiben Wang Design, Synthesis, and In Vivo and In Silico Evaluation of Coumarin Derivatives with Potential Antidepressant Effects Molecules coumarin synthesis antidepressant FST 5-HT molecular docking studies |
| title | Design, Synthesis, and In Vivo and In Silico Evaluation of Coumarin Derivatives with Potential Antidepressant Effects |
| title_full | Design, Synthesis, and In Vivo and In Silico Evaluation of Coumarin Derivatives with Potential Antidepressant Effects |
| title_fullStr | Design, Synthesis, and In Vivo and In Silico Evaluation of Coumarin Derivatives with Potential Antidepressant Effects |
| title_full_unstemmed | Design, Synthesis, and In Vivo and In Silico Evaluation of Coumarin Derivatives with Potential Antidepressant Effects |
| title_short | Design, Synthesis, and In Vivo and In Silico Evaluation of Coumarin Derivatives with Potential Antidepressant Effects |
| title_sort | design synthesis and in vivo and in silico evaluation of coumarin derivatives with potential antidepressant effects |
| topic | coumarin synthesis antidepressant FST 5-HT molecular docking studies |
| url | https://www.mdpi.com/1420-3049/26/18/5556 |
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