Discovery of novel N-substituted carbazoles as neuroprotective agents with potent anti-oxidative activity.
Discovery of novel N-substituted carbazoles as neuroprotective agents with potent anti-oxidative activity.
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DOI：
10.1016/j.ejmech.2013.07.029
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发表时间：
2013-10
影响因子：
6.7
通讯作者：
Daqian Zhu;Meihui Chen;Min Li;Bingling Luo;Yang Zhao;Peng Huang;F. Xue;S. Rapposelli;R. Pi;S. Wen
中科院分区：
文献类型：
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作者：
Daqian Zhu;Meihui Chen;Min Li;Bingling Luo;Yang Zhao;Peng Huang;F. Xue;S. Rapposelli;R. Pi;S. Wen
咔唑部分是一种重要的支架，具有多种生物学应用，例如抗氧化应激。我们之前合成的咔唑针对两种单独的氧化应激的神经保护特性进行了筛选。观察到一些新的咔唑衍生物对神经元细胞 HT22 具有中等至良好的神经保护作用，以防止谷氨酸或同型半胱氨酸 (HCA) 诱导的细胞损伤。引入咔唑环系统的取代基在其生物活性中起着至关重要的作用。特别是，大基团有利于化合物的神经保护活性。其中一种新化合物 6 显示出最佳的神经保护作用，这可能是由于其具有不依赖于谷胱甘肽 (GSH) 的机制的抗氧化活性。这些发现可能为开发用于治疗阿尔茨海默病等中枢神经系统疾病的新型咔唑衍生物提供替代策略。
Carbazole moiety is an important scaffold with a variety of biological applications, for example, anti-oxidative stress. Our previous synthesized carbazoles were screened for their neuroprotective properties against two individual oxidative stresses. Some of the new carbazole derivatives were observed with modest to good neuroprotective effects on neuronal cells HT22 against cell injury induced by glutamate or homocysteic acid (HCA). Substituents introduced to the carbazole ring system play crucial roles in their biological activities. In particular, a bulky group favors the neuroprotective activity of the compounds. One of the new compounds,6, showed the best neuroprotective effects, which might result from its anti-oxidative activity with a GSH-independent mechanism. These findings might provide an alternative strategy for the development of novel carbazole derivatives for the treatment of CNS diseases such as Alzheimer's disease.