目的：合成石杉碱甲新型衍生物并探索其神经保护作用。方法：石杉碱甲与不同取代基的磺酰氯反应合成一系列新型石杉碱甲衍生物,经熔点、电子自旋共振波谱联合质谱分析（electron spin resonance-mass spectrometry,ESR-MS）和氢核磁共振波谱法（hydrogen nuclear magnetic resonance spectroscopy,1H-NMR）等方法鉴定结构。运用淀粉样β蛋白片段25-35（β-amyloid peptide 25-35,Aβ25-35）诱导神经细胞SH-SY5Y损伤,通过四甲基偶氮唑盐比色法测定石杉碱甲新型衍生物对SH-SY5Y细胞的保护作用。结果：合成8个石杉碱磺酰基取代新型衍生物HA-1~HA-8,石杉碱甲、HA-4、HA-6和HA-7可逆转Aβ25-35对神经细胞SH-SY5Y的损伤,衍生物HA-4和HA-7活性优于石杉碱甲。结论：石杉碱甲新型衍生物HA-4和HA-7的神经保护作用优于母体石杉碱甲。
Abstract
Objective To synthesize novel (-) -huperzine A derivatives and explore their neuroprotective effects. Methods A series of (-) -huperzine A derivatives were synthesized through the reaction of (-) -huperzine A with multiple substituent sulfonyl chloride. Their structural information was extensively characterized by using melt point, ESR-MS and HRMS. Aβ25-35 was used to induce the nerve cell SH-SY5Y injury and apoptosis, and the neuroprotective effects of (-) -huperzine A and its novel derivatives was also evaluated on SH-SY5Y cells in vitro by using an MTT-assay. Results Eight novel (-) -huperzine A sulfonyl substituted derivatives HA-1 ~ HA-8 were synthesized. The (-) -huperzine A, HA-4, Ha-6 and HA-7 can reverse the injury of Aβ25-35 on SH-SY5Y cells. The activities of derivatives HA-4 and HA-7 were better than (-) -huperzine A. Conclusion The (-) -huperzine A derivatives HA-4 and HA-7 show better neuroprotective effects than (-) -huperzine A.
关键词
石杉碱甲 /
半合成 /
新型衍生物 /
神经保护
Key words
(-) -huperzine A /
semisynthesis /
novel derivatives /
neuroprotection
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参考文献
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