Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson’s Disease Models of Caenorhabditis elegans
Melatonin (MT) is a hormone with antioxidant activity secreted by the pineal gland in the human brain, which is highly efficient in scavenging free radicals and plays an important role in the neuro-immuno-endocrine system. Emerging evidence showed that MT supplementation was a potential therapeutic...
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Frontiers Media S.A.
2022-06-01
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| Series: | Frontiers in Chemistry |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fchem.2022.918116/full |
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| author | Li He Jing-Jing Du Jun-Jie Zhou Meng-Ting Chen Lu Luo Bao-Qiong Li Xiang-Zhi Zhang Wen-Zhe Ma Ai-Jun Ma Na Feng |
| author_facet | Li He Jing-Jing Du Jun-Jie Zhou Meng-Ting Chen Lu Luo Bao-Qiong Li Xiang-Zhi Zhang Wen-Zhe Ma Ai-Jun Ma Na Feng |
| author_sort | Li He |
| collection | DOAJ |
| description | Melatonin (MT) is a hormone with antioxidant activity secreted by the pineal gland in the human brain, which is highly efficient in scavenging free radicals and plays an important role in the neuro-immuno-endocrine system. Emerging evidence showed that MT supplementation was a potential therapeutic strategy for Parkinson’s disease (PD), which inhibits pathways associated with oxidative stress in PD. In this study, we reported a C7-selective olefination of melatonin under rhodium catalysis with the aid of PIII-directing groups and synthesized 10 new melatonin-C7-cinnamic acid derivatives (6a–6j). The antioxidant potential of the compounds was evaluated both by ABTS and ORAC methods. Among these newly synthesized melatonin derivatives, 6a showed significantly higher activity than MT at 10−5 M. In the transgenic Caenorhabditis elegans model of PD, 6a significantly reduces alpha-synuclein aggregation and dopaminergic neuronal damage in nematodes while reducing intracellular ROS levels and recovers behavioral dysfunction induced by dopaminergic neurodegeneration. Further study of the mechanism of action of this compound can provide new therapeutic ideas and treatment strategies for PD. |
| first_indexed | 2024-04-13T21:32:10Z |
| format | Article |
| id | doaj.art-1eb11b40ad3747bb8aec709c78f2a376 |
| institution | Directory Open Access Journal |
| issn | 2296-2646 |
| language | English |
| last_indexed | 2024-04-13T21:32:10Z |
| publishDate | 2022-06-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Chemistry |
| spelling | doaj.art-1eb11b40ad3747bb8aec709c78f2a3762022-12-22T02:29:06ZengFrontiers Media S.A.Frontiers in Chemistry2296-26462022-06-011010.3389/fchem.2022.918116918116Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson’s Disease Models of Caenorhabditis elegansLi He0Jing-Jing Du1Jun-Jie Zhou2Meng-Ting Chen3Lu Luo4Bao-Qiong Li5Xiang-Zhi Zhang6Wen-Zhe Ma7Ai-Jun Ma8Na Feng9School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaState Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Macau, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaSchool of Biotechnology and Health Sciences, Wuyi University, Jiangmen, ChinaMelatonin (MT) is a hormone with antioxidant activity secreted by the pineal gland in the human brain, which is highly efficient in scavenging free radicals and plays an important role in the neuro-immuno-endocrine system. Emerging evidence showed that MT supplementation was a potential therapeutic strategy for Parkinson’s disease (PD), which inhibits pathways associated with oxidative stress in PD. In this study, we reported a C7-selective olefination of melatonin under rhodium catalysis with the aid of PIII-directing groups and synthesized 10 new melatonin-C7-cinnamic acid derivatives (6a–6j). The antioxidant potential of the compounds was evaluated both by ABTS and ORAC methods. Among these newly synthesized melatonin derivatives, 6a showed significantly higher activity than MT at 10−5 M. In the transgenic Caenorhabditis elegans model of PD, 6a significantly reduces alpha-synuclein aggregation and dopaminergic neuronal damage in nematodes while reducing intracellular ROS levels and recovers behavioral dysfunction induced by dopaminergic neurodegeneration. Further study of the mechanism of action of this compound can provide new therapeutic ideas and treatment strategies for PD.https://www.frontiersin.org/articles/10.3389/fchem.2022.918116/fullderivative of melatoninsynthesisantioxidant activityC. elegansParkinson’s disease |
| spellingShingle | Li He Jing-Jing Du Jun-Jie Zhou Meng-Ting Chen Lu Luo Bao-Qiong Li Xiang-Zhi Zhang Wen-Zhe Ma Ai-Jun Ma Na Feng Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson’s Disease Models of Caenorhabditis elegans Frontiers in Chemistry derivative of melatonin synthesis antioxidant activity C. elegans Parkinson’s disease |
| title | Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson’s Disease Models of Caenorhabditis elegans |
| title_full | Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson’s Disease Models of Caenorhabditis elegans |
| title_fullStr | Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson’s Disease Models of Caenorhabditis elegans |
| title_full_unstemmed | Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson’s Disease Models of Caenorhabditis elegans |
| title_short | Synthesis of Melatonin Derivatives and the Neuroprotective Effects on Parkinson’s Disease Models of Caenorhabditis elegans |
| title_sort | synthesis of melatonin derivatives and the neuroprotective effects on parkinson s disease models of caenorhabditis elegans |
| topic | derivative of melatonin synthesis antioxidant activity C. elegans Parkinson’s disease |
| url | https://www.frontiersin.org/articles/10.3389/fchem.2022.918116/full |
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