title: Synthesis of antimitotic thioglycosides: in vitro and in vivo evaluation of their anticancer activity.
abstract: The synthesis and biological activity of oleylN-acetyl-α- and β-d-glucosaminides (1 and 2, respectively) and their thioglycosyl analogues (3 and 4, respectively) are reported. The compounds exhibited antimitotic activity on rat glioma (C6) and human lung carcinoma (A549) cell cultures in the micromolar range. Analysis of cell extracts using ultra performance liquid chromatography-mass spectrometry showed that the synthetic glycosides produce alterations in glycosphingolipid metabolism, with variable effect on the level of glucosylceramide depending on the configuration of the antimitotic used. In vivo experiments in nude mice bearing an implanted C6 glioma showed that the α-thioglycoside 3 reduced tumor volume, while the O-glycosyl derivative was inactive, highlighting the importance of using enzyme resistant glycosides.
authors.affiliation: Hospital Nacional de Parapléjicos,  SESCAM , Finca la Peraleda s/n, 45071 Toledo, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: García-Álvarez
authors.forename: Hugo
authors.initials: H
authors.lastname: Groult
authors.forename: Josefina
authors.initials: J
authors.lastname: Casas
authors.forename: M Asunción
authors.initials: MA
authors.lastname: Barreda-Manso
authors.forename: Natalia
authors.initials: N
authors.lastname: Yanguas-Casás
authors.forename: Manuel
authors.initials: M
authors.lastname: Nieto-Sampedro
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Romero-Ramírez
authors.forename: Alfonso
authors.initials: A
authors.lastname: Fernández-Mayoralas
mesh_terms: D000818:Animals; D050256:Antimitotic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D006017:Glycolipids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D006868:Hydrolysis; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D051381:Rats; D013329:Structure-Activity Relationship; D013863:Thioglucosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013865:Thioglycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000187:drug effects; D001619:beta-N-Acetylhexosaminidases / Q000737:chemistry
chemical_list: D050256:Antimitotic Agents; D006017:Glycolipids; D013863:Thioglucosides; D013865:Thioglycosides; C568521:oleyl 2-acetamido-2-deoxy-1-thioglucopyranoside; D001619:beta-N-Acetylhexosaminidases