红景天苷衍生物的合成及其抗缺氧活性

Synthesisand Anti-hypoxia Activities of Salidroside Derivatives

为了寻找安全、高效的抗缺氧活性分子,以对羟基苯乙醇和1,2,3,4,6-β-D-葡萄糖五乙酸酯为起始原料,设计合成了25个新型红景天苷衍生物R1~R10、X1~X10、J1~J5,其结构经1H NMR,13C NMR和HR-MS(ESI)表征,且均未见文献报道。采用H9C2心肌细胞缺氧/复氧模型对上述化合物进行体外抗缺氧活性评价,并通过人肾上皮细胞293T、人肺上皮细胞BEAS-2B、大鼠心肌细胞H9C2和人正常肝细胞LO2这4种细胞评价了体外抗缺氧活性较佳的化合物R7、X2、X8和J1的细胞毒性,最后通过常压缺氧小鼠模型,进一步评价了R7、X8和J1的体内抗缺氧活性。结果表明:R7、X8和J1表现出显著的体内外抗缺氧活性且无明显的细胞毒性。

In order to find safe and effective anti-hypoxic molecules,a series of 25 novel salidroside derivatives R1~R10,X1~X10 and J1~J5 were designed and synthesized using p-hydroxyphenylethanol and 1,2,3,4,6-β-D-glucosaccharide pentaacetate as starting materials.Their structures were confirmed by~1H NMR,13C NMR and HR-MS(ESI),which have not been reported in the literature.The anti-hypoxia activities of the target compounds were evaluated by the hypoxia/reoxygenation model of H9C2 cardiomyocytes in vitro,then the cytotoxicities of R7,X2,X8 and J1 to human renal epithelial cells 293T,human lung epithelial cells BEAS-2B,rat cardiomyocytes H9C2 and human normal hepatocytes LO2 were evaluated.Finally,the in vivo anti-hypoxia activities of R7,X8 and J1 were further evaluated by atmospheric hypoxia mouse model.The results showed that R7,X8 and J1 exhibited significant anti-hypoxia activities in vitro and in vivo without significant cytotoxicity.