New 6-amino-6-deoxy-glycoglycerolipids derived from 2-O-β-d-glucopyranosylglycerol: insights into the structure–activity relationship of glycoglycerolipids as anti-tumor promoters

•6-Amino-6-deoxyglycoglycerolipids based on 2-O-β-d-glucosylglycerol were synthesized.•Compounds were tested for their in vitro and in vivo anti-tumor-promoting activity.•Compounds resulted less active than previously studied glycoglycerolipids.•The presence of the nitrogen atom strongly reduced the activity of the compounds.•In general 6-position of the sugar plays a crucial role in glycoglycerolipid activity.

As part of a project aimed at obtaining compounds capable of inhibiting tumor promotion, new 6-amino-6-deoxyglycoglycerolipids (AGGLs) derived from 2-O-β-d-glucopyranosyl-sn-glycerol were synthesized and tested for their anti-tumor-promoting activity using a short-term in vitro assay of the inhibition of Epstein–Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). The corresponding 6-amino-6-deoxy-β-d-octylglucosides were also prepared as simplified aminoglycolipid models and tested. Comparison with the activity of a series of previously studied glycoglycerolipids showed that replacing the 6-oxygen of the glucose moiety by a nitrogen atom greatly reduced the in vitro activity of the compounds. A two-stage mouse skin carcinogenesis test of two representative aminoglycoglycerolipids confirmed their reduced activity also in this in vivo model.

Graphical abstractCompounds 1–4 were prepared and their anti-tumor-promoting activity tested through a short term in vitro assay for the inhibition of EBV activation induced by TPA.Figure optionsDownload full-size imageDownload as PowerPoint slide