title: Ameliorated or Acquired Cytostatic/Cytotoxic Properties of Nucleosides by Lipophilization.
abstract: A series of nucleolipids, containing one of the β-D-ribonucleosides 5-fluorouridine, 6-azauridine, uridine, or 5-methyluridine were lipophilized, either at the O-2',3'-position and/or at N(3) of the nucleobase with a large variety of hydrophobic residues. The resulting nucleolipids as well as the parent nucleosides and the lipid precursors were investigated in vitro with respect to their antitumor activity towards i) ten human tumor cell lines from the NCI 60 panel and ii) partly against three further tumor cell lines, namely a) human astrocytoma/oligodendro glioma GOs-3, b) rat malignantneuroectodermal BT4Ca, and c) differentiated human THP-1 macrophages. Inspection of the doseresponse curves allows two main conclusions concerning lipid determinants lending the corresponding nucleoside an ameliorated or an acquired antitumor activity: i) introduction of either a symmetrical O-2',3'-nonadecylidene ketal group or introduction of an O-2',3'-ethyl levulinate moiety plus an N(3)-farnesyl group leads often to nucleolipids with significant cytostatic/cytotoxic properties; ii) for the two canonical and non-toxic nucleosides uridine and 5-methyluridine, the condensation with also non-toxic lipids gives nucleolipids with a pronounced antitumor activity.
authors.affiliation: Organic Chemistry I - Bioorganic Chemistry, Institute of Chemistry of New Materials, University of Osnabrück, Barbarastr. 7, DE-49069 Osnabrück.|Fraunhofer Institute for Molecular Biology and Applied Ecology IME, Department ScreeningPort, Schnackenburgallee 114, DE-22525 Hamburg.
authors.forename: Christine
authors.initials: C
authors.lastname: Knies
authors.affiliation: Anatomy and Cell Biology, Department of Medical Cell Biology, University of Marburg, Robert-Koch-Strasse 8, DE-35032 Marburg.
authors.forename: Gabriel
authors.initials: G
authors.lastname: Bonaterra
authors.affiliation: Anatomy and Cell Biology, Department of Medical Cell Biology, University of Marburg, Robert-Koch-Strasse 8, DE-35032 Marburg.
authors.forename: Katharina
authors.initials: K
authors.lastname: Hammerbacher
authors.affiliation: Anatomy and Cell Biology, Department of Medical Cell Biology, University of Marburg, Robert-Koch-Strasse 8, DE-35032 Marburg.
authors.forename: Andrea
authors.initials: A
authors.lastname: Cordes
authors.affiliation: Anatomy and Cell Biology, Department of Medical Cell Biology, University of Marburg, Robert-Koch-Strasse 8, DE-35032 Marburg.
authors.forename: Ralf
authors.initials: R
authors.lastname: Kinscherf
authors.affiliation: Organic Chemistry I - Bioorganic Chemistry, Institute of Chemistry of New Materials, University of Osnabrück, Barbarastr. 7, DE-49069 Osnabrück. Helmut.Rosemeyer@uos.de.
authors.forename: Helmut
authors.initials: H
authors.lastname: Rosemeyer
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D054697:Cytostatic Agents / Q000737:chemistry* / Q000494:pharmacology; D003603:Cytotoxins / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008055:Lipids / Q000737:chemistry*; D015394:Molecular Structure; D009705:Nucleosides / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats
chemical_list: D054697:Cytostatic Agents; D003603:Cytotoxins; D008055:Lipids; D009705:Nucleosides
keywords: Cytotoxic/cytostatic activity; NCI 60 Tumor cell lines; Nucleolipids