Influence of the configurational pattern of sp(2)-iminosugar pseudo N-, S-, O- and C-glycosides on their glycoside inhibitory and antitumor properties.

Autor: Sánchez-Fernández EM; Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Sevilla, Spain. Electronic address: esanchez4@us.es., Gonçalves-Pereira R; Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Sevilla, Spain., Rísquez-Cuadro R; Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Sevilla, Spain., Plata GB; BioLab, Instituto Universitario de Bio-Orgánica 'Antonio González', Centro de Investigaciones Biomédicas de Canarias, Universidad de La Laguna, 38206 La Laguna, Spain., Padrón JM; BioLab, Instituto Universitario de Bio-Orgánica 'Antonio González', Centro de Investigaciones Biomédicas de Canarias, Universidad de La Laguna, 38206 La Laguna, Spain., García Fernández JM; Instituto de Investigaciones Químicas (IIQ), CSIC-Universidad de Sevilla, Avda. Américo Vespucio 49, 41092 Sevilla, Spain., Ortiz Mellet C; Departamento de Química Orgánica, Facultad de Química, Universidad de Sevilla, Profesor García González 1, 41012 Sevilla, Spain. Electronic address: mellet@us.es.
Jazyk: angličtina
Zdroj: Carbohydrate research [Carbohydr Res] 2016 Jun 24; Vol. 429, pp. 113-22. Date of Electronic Publication: 2016 Jan 21.
DOI: 10.1016/j.carres.2016.01.006
Abstrakt: 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.
(Copyright © 2016 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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