title: Influence of the configurational pattern of sp(2)-iminosugar pseudo N-, S-, O- and C-glycosides on their glycoside inhibitory and antitumor properties.
abstract: The synthesis of a complete series of cyclic carbamate-type sp(2)-iminosugar N-, S-, O- and C-octyl pseudoglycosides related to nojirimycin, mannojirimycin and galactonojirimycin, all having the α-pseudoanomeric configuration, is reported. The gem-diamine-type N-pseudoglycosides can be accessed directly from the corresponding reducing sp(2)-imisosugar precursors by reaction with octylamine in methanol, whereas per-O-acetyl or 1-fluoro derivatives were used as pseudoglycosyl donors for the preparation of S-pseudoglycosides or O- and C-pseudoglycosides, respectively. Evaluation of their inhibitory properties against a panel of glycosidases evidenced selectivity profiles that strongly depend on the configurational pattern and the nature of the glycosidic linkage. On the contrary, the antiproliferative activity determined against a panel of tumor cell lines was largely independent of the relative orientation of the hydroxyl groups in the sp(2)-iminosugar moiety. Indeed, sp(2)-iminosugar representatives exhibiting significant growth inhibition potencies were identified in all three configurationally different types of compounds studied, namely α-d-gluco, α-d-manno and α-d-galacto glycoside analogs. Interestingly, none of the compounds affected viability and mortality of normal cells at the used concentrations. Altogether, the results strongly suggest that the anticancer activity of amphiphilic sp(2)-iminosugar glycosides might be unrelated, or not solely related, to their glycosidase inhibitory activity.
authors: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Sevilla, Spain. Electronic address: esanchez4@us.es.
authors: Elena M
authors: EM
authors: Sánchez-Fernández
authors: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Sevilla, Spain.
authors: Rita
authors: R
authors: Gonçalves-Pereira
authors: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Sevilla, Spain.
authors: Rocío
authors: R
authors: Rísquez-Cuadro
authors: BioLab, Instituto Universitario de Bio-Orgánica "Antonio González", Centro de Investigaciones Biomédicas de Canarias, Universidad de La Laguna, 38206 La Laguna, Spain.
authors: Gabriela B
authors: GB
authors: Plata
authors: BioLab, Instituto Universitario de Bio-Orgánica "Antonio González", Centro de Investigaciones Biomédicas de Canarias, Universidad de La Laguna, 38206 La Laguna, Spain.
authors: José M
authors: JM
authors: Padrón
authors: Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Avda. Américo Vespucio 49, 41092 Sevilla, Spain.
authors: José M
authors: JM
authors: García Fernández
authors: Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Sevilla, Spain. Electronic address: mellet@us.es.
authors: Carmen
authors: C
authors: Ortiz Mellet
mesh_terms: D000588:Amines / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D005690:Galactose / Q000031:analogs & derivatives; D005947:Glucose / Q000031:analogs & derivatives; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D006027:Glycosides / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D050111:Imino Sugars / Q000138:chemical synthesis* / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D008358:Mannose / Q000031:analogs & derivatives; D000432:Methanol / Q000737:chemistry; D009928:Organ Specificity; D013329:Structure-Activity Relationship
chemical_list: D000588:Amines; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D006027:Glycosides; D050111:Imino Sugars; D006026:Glycoside Hydrolases; D005947:Glucose; D008358:Mannose; C008699:octylamine; D005690:Galactose; D000432:Methanol
keywords: Antitumor activity; Glycosidase inhibitor; Glycosides; Nojirimycin; sp(2)-Iminosugar