Synthesis and bioassay of β-（1,4）-D-mannans as potential agents against Alzheimer＇s disease  

作　　者：Ru-wei JIANG Xiao-guang DU Xuan ZHANG Xin WANG Ding-yu HU Tao MENG Yue-lei CHEN Mei-yu GENG Jing-kang SHEN 

机构地区：[1]State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai 201203, China

出　　处：《Acta Pharmacologica Sinica》2013年第12期1585-1591,共7页中国药理学报（英文版）

摘　　要：Aim： Oligomannurarate 971 derived from a marine plant has shown neuroprotective effects. In this study we synthesized a series of truncated derivatives of the oligosaccharide, and investigated the effect of these derivatives against Aβ peptide toxicity in vitro. Methods： The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with Aβ1-40 （2 pmol/L）, and the cell viability was detected using a CCK8 assay. Results： A series of β-（1,4）-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 pmol/L β-（1,4）-D-mannobiose 6, β-（1,4）-D-mannotriose 9 or β-（1,4）-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated Aβ1-40-induced toxicity. The efficacies were similar to those caused by 10 pmol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active. Conclusion： Synthetic homogeneous short chain β-（1,4）-D-mannans shows neuroprotective effect against Aβ peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed.Aim： Oligomannurarate 971 derived from a marine plant has shown neuroprotective effects. In this study we synthesized a series of truncated derivatives of the oligosaccharide, and investigated the effect of these derivatives against Aβ peptide toxicity in vitro. Methods： The sulfoxide method was applied to synthesize the derivatives. SH-SY5Y human neuroblastoma cells were treated with Aβ1-40 （2 pmol/L）, and the cell viability was detected using a CCK8 assay. Results： A series of β-（1,4）-D-mannosyl oligosaccharide, ranging from the disaccharide to the hexasaccharide, were synthesized. Addition of 10 pmol/L β-（1,4）-D-mannobiose 6, β-（1,4）-D-mannotriose 9 or β-（1,4）-D-mannotetraose 12 in SH-SY5Y cells significantly attenuated Aβ1-40-induced toxicity. The efficacies were similar to those caused by 10 pmol/L oligomannurarate 971 or alzhemed. Other oligosaccharides including oligomaltoses and oligocelluloses were less active. Conclusion： Synthetic homogeneous short chain β-（1,4）-D-mannans shows neuroprotective effect against Aβ peptide toxicity similar to that of heterogeneous oligomannurarate 971 and alzhemed.

关 键 词：Alzheimer＇s disease Aβ peptide OLIGOSACCHARIDE β-（1 4）-D-mannan oligomannurarate 971 alzhemed NEUROPROTECTION medicinal chemistry 

分 类 号：Q421[生物学—神经生物学] TS245.9[生物学—生理学]