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Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents
Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI t...
Autores principales: | , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437665/ https://www.ncbi.nlm.nih.gov/pubmed/30972281 http://dx.doi.org/10.1016/j.apsb.2019.01.003 |
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author | Wang, Jiabing Huang, Lili Cheng, Chanchan Li, Ge Xie, Jingwen Shen, Mengya Chen, Qian Li, Wulan He, Wenfei Qiu, Peihong Wu, Jianzhang |
author_facet | Wang, Jiabing Huang, Lili Cheng, Chanchan Li, Ge Xie, Jingwen Shen, Mengya Chen, Qian Li, Wulan He, Wenfei Qiu, Peihong Wu, Jianzhang |
author_sort | Wang, Jiabing |
collection | PubMed |
description | Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H(2)O(2)-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 could emerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment. |
format | Online Article Text |
id | pubmed-6437665 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-64376652019-04-10 Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents Wang, Jiabing Huang, Lili Cheng, Chanchan Li, Ge Xie, Jingwen Shen, Mengya Chen, Qian Li, Wulan He, Wenfei Qiu, Peihong Wu, Jianzhang Acta Pharm Sin B Original article Scavenging reactive oxygen species (ROS) by antioxidants is the important therapy to cerebral ischemia-reperfusion injury (CIRI) in stroke. The antioxidant with novel dual-antioxidant mechanism of directly scavenging ROS and indirectly through antioxidant pathway activation may be a promising CIRI therapeutic strategy. In our study, a series of chalcone analogues were designed and synthesized, and multiple potential chalcone analogues with dual antioxidant mechanisms were screened. Among these compounds, the most active 33 not only conferred cytoprotection of H(2)O(2)-induced oxidative damage in PC12 cells through scavenging free radicals directly and activating NRF2/ARE antioxidant pathway at the same time, but also played an important role against ischemia/reperfusion-related brain injury in animals. More importantly, in comparison with mono-antioxidant mechanism compounds, 33 exhibited higher cytoprotective and neuroprotective potential in vitro and in vivo. Overall, our findings showed compound 33 could emerge as a promising anti-ischemic stroke drug candidate and provided novel dual-antioxidant mechanism strategies and concepts for oxidative stress-related diseases treatment. Elsevier 2019-03 2019-01-07 /pmc/articles/PMC6437665/ /pubmed/30972281 http://dx.doi.org/10.1016/j.apsb.2019.01.003 Text en © 2019 Chinese Pharmaceutical Association and Institute of Materia Medica, Chinese Academy of Medical Sciences. Production and hosting by Elsevier B.V. http://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Original article Wang, Jiabing Huang, Lili Cheng, Chanchan Li, Ge Xie, Jingwen Shen, Mengya Chen, Qian Li, Wulan He, Wenfei Qiu, Peihong Wu, Jianzhang Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents |
title | Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents |
title_full | Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents |
title_fullStr | Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents |
title_full_unstemmed | Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents |
title_short | Design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents |
title_sort | design, synthesis and biological evaluation of chalcone analogues with novel dual antioxidant mechanisms as potential anti-ischemic stroke agents |
topic | Original article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6437665/ https://www.ncbi.nlm.nih.gov/pubmed/30972281 http://dx.doi.org/10.1016/j.apsb.2019.01.003 |
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