Department of Natural Products Chemistry, School of Pharmacy, Fudan University, 826 Zhangheng Road, Shanghai 201203, China.
Bioorg Med Chem Lett. 2013 Mar 15;23(6):1793-6. doi: 10.1016/j.bmcl.2013.01.038. Epub 2013 Jan 23.
A series of mercaptoethylleonurine and mercaptoethylguanidine derivatives were designed and synthesized. Their neuroprotective effects toward H2O2-induced apoptosis were investigated in human SH-SY5Y cells. The results from these studies identified several potent compounds, with compound 8k emerging as the most effective. Further investigation demonstrated that 8k reduced H2O2-induced activation of mitochondrial apoptosis by inhibiting the expression of Bax and elevating the expression of Bcl-2. Moreover, the molecular mechanism underlying the observed neuroprotective effects of 8k was exerted via the Akt and JNK pathways. Compound 8k can be a lead compound for further discovery of neuroprotective medicine.
设计并合成了一系列巯基乙撑莱菔氨酸和巯基乙撑胍衍生物。研究了它们对人 SH-SY5Y 细胞中 H2O2 诱导的细胞凋亡的神经保护作用。这些研究结果确定了几种有效化合物，其中化合物 8k 最为有效。进一步的研究表明，8k 通过抑制 Bax 的表达和提高 Bcl-2 的表达来抑制 H2O2 诱导的线粒体凋亡的激活。此外，观察到的 8k 的神经保护作用的分子机制是通过 Akt 和 JNK 途径发挥的。化合物 8k 可以作为进一步发现神经保护药物的先导化合物。
