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

Abstract

AbstractMannosylerythritol 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.