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Design, synthesis, and biological evaluation of novel stachydrine derivatives as potent neuroprotective agents for cerebral ischemic stroke

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Abstract

Stachydrine is a natural product with multiple protective biological activities, including those involved in preventing cancer, ischemia, and cardiovascular disease. However, its use has been limited by low bioavailability and unsatisfactory efficacy. To address this problem, a series of stachydrine derivatives (A1/A2/A3/A4/B1/B2/B3/B4) were designed and synthesized, and biological studies were carried out in vitro and in vivo. When compared with stachydrine, Compound B1 exhibited better neuroprotective effects in vitro, and significantly reduced infarction size in the model of the middle cerebral artery occlusion rat model. Therefore, Compound B1 was selected for further research on ischemic stroke.

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Funding

This study was funded by the “Zhufeng Scholar Program” of the Ocean University of China (841412016), the “Major Projects of Independent Innovation” of Qingdao (15-4-13-zdzx-hy), the “Outstanding Talents Plan” of Qingdao (15-10-3-15-(34)-zch), and the Aoshan Talents Training Program of Qingdao National Laboratory for Marine Science and Technology (No. 2017ASTCP-OS08) to Dr. Wenbao Li.

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Authors and Affiliations

  1. School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003, China

    Liang Zhang, Chenhui Hou, Sifeng Zhu, Lili Zhong, Jianchun Zhao & Wenbao Li

  2. Shandong Peninsula Engineering Research Center of Comprehensive Brine Utilization, Weifang University of Science and Technology, Weifang, 262700, Shandong, People’s Republic of China

    Feng Li

  3. Department of Medicine and Pharmacy, Ocean University of China, 23 HongKong Road, Qingdao, 266071, People’s Republic of China

    Feng Li

  4. Marine Biomedical Research Institute of Qingdao, Qingdao, 266071, China

    Jianchun Zhao & Wenbao Li

  5. Shenzhen Institute, Guangdong Ocean University, Shenzhen, 518116, China

    Cai Song

  6. Innovation Center for Marine Drug Screening and Evaluation, Qingdao National Laboratory for Marine Science and Technology, Qingdao, 266071, China

    Wenbao Li

Authors
  1. Liang Zhang
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  2. Feng Li
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  3. Chenhui Hou
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  4. Sifeng Zhu
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  5. Lili Zhong
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  6. Jianchun Zhao
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  7. Cai Song
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  8. Wenbao Li
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Contributions

Wenbao Li and Feng Li conceived and designed research. Liang Zhang, Chenhui Hou, and Sifeng Zhu conducted experiments. Lili Zhong, Jianchun Zhao, and Cai Song made contribution in ex vivo and in vivo studies. Liang Zhang and Chenhui Hou analyzed data. Liang Zhang wrote the manuscript. All authors read and approved the manuscript. We explicitly state that the data were generated in-house, and we did not use a paper mill.

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Correspondence to Feng Li or Wenbao Li.

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Zhang, L., Li, F., Hou, C. et al. Design, synthesis, and biological evaluation of novel stachydrine derivatives as potent neuroprotective agents for cerebral ischemic stroke. Naunyn-Schmiedeberg's Arch Pharmacol 393, 2529–2542 (2020). https://doi.org/10.1007/s00210-020-01868-4

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  • DOI: https://doi.org/10.1007/s00210-020-01868-4

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