Designed Mannosylerythritol Lipid Analogues Exhibiting Both Selective Cytotoxicity Against Human Skin Cancer Cells and Recovery Effects on Damaged Skin Cells

Mannosylerythritol lipids (MELs) are a class of amphipathic molecules bearing a hydrophilic 4-O-beta-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 alpha-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. We report the synthesis of four kinds of mannosylerythritol lipid (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 alpha-S-MEL-A ([2S,3R]-erythritol type) and their selective cytotoxicity against HSC-5 cancer cells. The results indicate that R-MTL-A has potential as a lead compound for new cosmeceuticals exhibiting both cancer cell-selective toxicity and recovery effects on damaged skin cells. image