title: 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.
abstract: 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.
authors.affiliation: Department of Medical Biotechnology and Translational Medicine, University of Milano, Milano, Italy. diego.colombo@unimi.it
authors.forename: Diego
authors.initials: D
authors.lastname: Colombo
authors.forename: Clarissa
authors.initials: C
authors.lastname: Gagliardi
authors.forename: Maria
authors.initials: M
authors.lastname: Vetro
authors.forename: Fiamma
authors.initials: F
authors.lastname: Ronchetti
authors.forename: Midori
authors.initials: M
authors.lastname: Takasaki
authors.forename: Takao
authors.initials: T
authors.lastname: Konoshima
authors.forename: Nobutaka
authors.initials: N
authors.lastname: Suzuki
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
mesh_terms: D000818:Animals; D000956:Antigens, Viral; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D005260:Female; D005960:Glucosides / Q000737:chemistry*; D006017:Glycolipids / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D009303:Nasopharyngeal Neoplasms / Q000188:drug therapy / Q000821:virology; D009584:Nitrogen / Q000737:chemistry; D010100:Oxygen / Q000737:chemistry; D010212:Papilloma / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000188:drug therapy / Q000473:pathology; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000009:adverse effects; D014407:Tumor Cells, Cultured
chemical_list: D000956:Antigens, Viral; D000970:Antineoplastic Agents; C033305:Epstein-Barr virus early antigen; D005960:Glucosides; D006017:Glycolipids; C034727:glucosylglycerol; C015903:glycerolglycolipids; D009584:Nitrogen; D013755:Tetradecanoylphorbol Acetate; D010100:Oxygen