Design, Synthesis, and Biological Evaluation of Ganglioside Hp-s1 Analogues Varying at Glucosyl Moiety

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• 作者：Jung-Tung Hung ; Chun-Hong Yeh ; Shih-An Yang ; Chiu-Ya Lin ; Hung-Ju Tai ; Ganesh B. Shelke ; Daggula Mallikarjuna Reddy ; Alice L. Yu ; Shun-Yuan Luo
• 刊名：ACS Chemical Neuroscience
• 出版年：2016
• 出版时间：August 17, 2016
• 年：2016
• 卷：7
• 期：8
• 页码：1107-1111
• 全文大小：364K
• 年卷期：0
• ISSN：1948-7193

文摘

Ganglioside Hp-s1 is isolated from the ovary of sea urchin Diadema setosum. It exhibited better neuritogenic activity than GM1 in pheochromocytoma 12 cells. To explore the roles of glucosyl moiety of Hp-s1 in contributing to the neurogenic activity, we developed feasible procedures for synthesis of Hp-s1 analogues (2a–2f). The glucosyl moiety of Hp-s1 was replaced with α-glucose, α-galactose, β-galactose, α-mannose, and β-mannose, and their biological activities on SH-SY5Y cells and natural killer T (NKT) cells were evaluated. We found that the orientation of C-2 hydroxyl group at glucosyl moiety of Hp-s1 plays an important role to induce neurite outgrowth of SH-SY5Y cells. Surprisingly, compound 2d could activate NKT cells to produce interleukin 2, although it did not show great activity on neurite outgrowth of SH-SY5Y cells. In general, the Hp-s1 might be considered as a lead compound for the development of novel drugs aimed at modulating the activity of neuronal cells.