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European journal of medicinal chemistry v.143, 2018년, pp.438 - 448   SCI SCIE
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Pyrano[3,2-a]carbazole alkaloids as effective agents against ischemic stroke in vitro and in vivo

Zang, Yingda (Corresponding author. ) ; Song, Xiuyun (Corresponding author. ) ; Li, Chuangjun ; Ma, Jie ; Chu, Shifeng ; Liu, Dandan ; Ren, Qian ; Li, Yan ; Chen, Naihong ; Zhang, Dongming ;
  • 초록  

    Abstract A series of pyrano[3,2- a ]carbazole alkaloids were designed and synthesized as analogues of Claulansine F (Clau F, 10a ) isolated from Clausena lansium . Some of compounds showed strong neuroprotective effects and were promising agents against ischemic stroke. Among these compounds, 7c was the most active in inhibiting the programmed death of PC12 cells and primary cortical neurons. This compound induced neuroprotection following ischemic reperfusion and decreased neurological deficit scores in treated animals. Furthermore, 7c could penetrate the blood-brain barrier (BBB) in rats, and its exposure in the brain was 4.3-fold higher than that in plasma. More importantly, compared to edaravone, 7c exhibited stronger free radical scavenging activity. Our findings suggest that 7c may be promising for further evaluation as an intervention for ischemic stroke. Highlights A series of pyrano[3,2- a ]carbazole alkaloids were designed and synthesized as analogues of Claulansine F. 7c was the most active in inhibiting the programmed death of PC12 cells and primary cortical neurons. 7c induced neuroprotection following ischemic reperfusion and decreased neurological deficit scores in treated animals. 7c could penetrate the blood-brain barrier (BBB) in rats. 7c exhibited stronger free radical scavenging activity compared to Edaravone. Graphical abstract [DISPLAY OMISSION]


  • 주제어

    Pyrano[3,2-a]carbazole alkaloids .   Neuroprotection .   Ischemic stroke.  

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