Synthesis and biological evaluation of memantine nitrates as a potential treatment for neurodegenerative diseases
Synthesis and biological evaluation of memantine nitrates as a potential treatment for neurodegenerative diseases
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硝酸美金刚作为神经退行性疾病潜在治疗方法的合成和生物学评价
DOI：
10.1039/c6md00509h
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发表时间：
2017-01-01
期刊：
影响因子：
--
通讯作者：
Wang, Yuqiang
中科院分区：
文献类型：
--
作者：
Liu, Zheng;Yang, Si;Wang, Yuqiang
设计并合成了一系列硝酸美金刚衍生物，作为对神经退行性疾病具有神经保护和血管舒张活性的双功能化合物。这些化合物结合了美金刚骨架和硝酸盐部分，从而抑制中枢神经系统中的N-甲基-D-天冬氨酸受体并释放NO。生物学评价结果表明，新型硝酸美金刚在体外可有效保护神经元免受谷氨酸诱导的损伤。此外，硝酸美金刚可以扩张主动脉环，对抗去氧肾上腺素引起的收缩。分析了神经保护和血管舒张的结构-活性关系。在进一步的研究中，化合物 MN-05 通过抑制 Ca2+ 内流、减少自由基产生并维持线粒体膜电位来显着保护皮质神经元。有必要对 MN-05 进行进一步研究。
A series of memantine nitrate derivatives, as dual functional compounds with neuroprotective and vasodilatory activity for neurodegenerative diseases, was designed and synthesized. These compounds combined the memantine skeleton and a nitrate moiety, and thus inhibited the N-methyl-D-aspartic acid receptor and released NO in the central nervous system. The biological evaluation results revealed that the new memantine nitrates were effective in protecting neurons against glutamate-induced injury in vitro. Moreover, memantine nitrates dilated aortic rings against phenylephrine-induced contraction. The structure- activity relationships of neuroprotection and vasodilation were both analyzed. In further studies, compound MN-05 significantly protected cortical neurons by inhibiting Ca2+ influx, reducing free radical production and maintaining the mitochondrial membrane potential. Further research on MN-05 is warranted.