Abstract：
Mannosylerythritol lipids (MELs) are a class of amphipathic molecules bearing a hydrophilic 4-O-β-D-mannopyranosyl-D-erythritol skeleton. Here, we designed and synthesized four kinds of MEL analogues R-MEL-A ([2R,3S]-erythritol type), S-mannosylthreitol lipid (MTL)-A ([2S,3S]-threitol type), R-MTL-A ([2R,3R]-threitol type), and α-S-MEL-A ([2S,3R]-erythritol type) using our previously reported boron-mediated aglycon delivery (BMAD) method and a neighboring group assisted glycosylation method. The selective cytotoxicity of the target compounds against cancer cells was evaluated, with R-MTL-A showing the highest selective cytotoxicity against human skin squamous carcinoma HSC-5 cells. Our findings suggest that R-MTL-A induces necrosis-like cell death against HSC-5 cells by decreasing cell membrane fluidity. R-MTL-A also exhibits an efficient recovery effect on damaged skin cells, indicating that R-MTL-A has potential as a lead compound for new cosmeceuticals with both cancer cell-selective toxicity and recovery effects on damaged skin cells.
摘要：
甘露赤藓糖醇脂质(MEL)是一类具有亲水性4-O-β-D-吡喃甘露糖基-D-赤藓糖醇骨架的两亲分子。这里,我们设计并合成了四种MEL类似物R-MEL-A（[2R，3S]-赤藓糖醇型)，S-甘露糖苏糖醇脂质（MTL）-A（[2S，3S]-苏糖醇型)，R-MTL-A([2R,3R]-苏糖醇型)，和α-S-MEL-A([2S，3R]-赤藓糖醇型）使用我们先前报道的硼介导的糖苷配基递送（BMAD）方法和相邻组辅助的糖基化方法。评价了目标化合物对癌细胞的选择性细胞毒性，R-MTL-A对人皮肤鳞状细胞癌HSC-5细胞具有最高的选择性细胞毒性。我们的发现表明，R-MTL-A通过降低细胞膜流动性来诱导针对HSC-5细胞的坏死样细胞死亡。R-MTL-A还对受损的皮肤细胞具有有效的恢复作用，表明R-MTL-A具有作为新型药妆的先导化合物的潜力，同时具有癌细胞选择性毒性和对受损皮肤细胞的恢复作用。
