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

As part of a project aimed at obtaining compounds capable of inhibiting tumor promotion, new 6-amino-6-deoxyglycoglycerolipids (AGGLs) derived from 2-O-beta-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-beta-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. (C) 2013 Elsevier Ltd. All rights reserved.