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

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. Graphical abstract.

• Authors: Liang Zhang, Feng Li, Chenhui Hou, Sifeng Zhu, Lili Zhong, Jianchun Zhao, Cai Song, Wenbao Li
• Journal: Naunyn-Schmiedeberg's archives of pharmacology (Naunyn Schmiedebergs Arch Pharmacol) Vol. 393 Issue 12 Pg. 2529-2542 (12 2020) ISSN: 1432-1912 [Electronic] Germany
• PMID: 32372350 (Publication Type: Journal Article)

Chemical References

• Neuroprotective Agents
• Proline
• stachydrine

Topics

• Animals
• Animals, Newborn
• Brain Ischemia (metabolism, prevention & control)
• Cell Survival (drug effects, physiology)
• Cells, Cultured
• Drug Design
• Drug Evaluation, Preclinical (methods)
• Ischemic Stroke (metabolism, prevention & control)
• Neuroprotective Agents (chemical synthesis, therapeutic use)
• Proline (analogs & derivatives, chemical synthesis, therapeutic use)
• Rats
• Rats, Sprague-Dawley