Novel hybrids of 3-n-butylphthalide and edaravone: Design, synthesis and evaluations as potential anti-ischemic stroke agents.

Abstract

Fourteen hybrids (10a-g, 11a-g) of 3-n-butylphthalide (NBP) and edaravone (Eda) analogues have been designed and synthesized as potential anti-ischemic stroke agents. In vitro biological studies showed that compounds 10d and 10g exhibited more potent anti-platelet aggregation than ticlopidine (Ticlid), aspirin (ASP) and NBP. Compound 10g more significantly prevented H2O2-mediated neuronal cell (PC12) death than NBP, Eda or NBP together with Eda. Meanwhile, 10g also possessed potent radical scavenging effects on hydroxyl radical (˙OH) and superoxide anion radical (˙O2(-)). Our findings may provide new insights into the development of these hybrids, like 10g, for the intervention of ischemic stroke.

• Authors: Xiao Sheng, Kai Hua, Chunyu Yang, Xiaoli Wang, Hui Ji, Jinyi Xu, Zhangjian Huang, Yihua Zhang
• Journal: Bioorganic & medicinal chemistry letters (Bioorg Med Chem Lett) Vol. 25 Issue 17 Pg. 3535-40 (Sep 01 2015) ISSN: 1464-3405 [Electronic] England
• PMID: 26189079 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Benzofurans
• Free Radical Scavengers
• Neuroprotective Agents
• Platelet Aggregation Inhibitors
• 3-n-butylphthalide
• Hydrogen Peroxide
• Edaravone
• Antipyrine

Topics

• Animals
• Antipyrine (analogs & derivatives, chemistry, pharmacology)
• Benzofurans (chemistry, pharmacology)
• Cell Line
• Drug Design
• Edaravone
• Free Radical Scavengers (chemistry, pharmacology)
• Humans
• Hydrogen Peroxide (metabolism)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (chemistry, pharmacology)
• Platelet Aggregation (drug effects)
• Platelet Aggregation Inhibitors (chemistry, pharmacology)
• Rats
• Stroke (drug therapy)