Novel Nucleolipids of Pyrimidine beta-D-Ribonucleosides: Combinatorial Synthesis, Spectroscopic Characterization, and Cytostatic/Cytotoxic Activities
Autor(en): | Knies, Christine Hammerbacher, Katharina Bonaterra, Gabriel A. Kinscherf, Ralf Rosemeyer, Helmut |
Stichwörter: | 5-FLUOROURIDINE; ACETAL DERIVATIVES; ADENOSINE; Biochemistry & Molecular Biology; BT4Ca; BUILDING-BLOCKS; CARCINOMA CELLS; Chemistry; Chemistry, Multidisciplinary; Combinatorial synthesis; Cytostatic; cytotoxic activity; DRUG; GOS-3; IDENTIFICATION; IMMOBILIZATION; LIPOPHILIZATION; Nucleolipids; NUCLEOSIDES; THP-1 | Erscheinungsdatum: | 2016 | Herausgeber: | WILEY-V C H VERLAG GMBH | Journal: | CHEMISTRY & BIODIVERSITY | Volumen: | 13 | Ausgabe: | 2 | Startseite: | 160 | Seitenende: | 180 | Zusammenfassung: | Four series of nucleolipids with either uridine, 5-methyluridine, 5-fluorouridine, and 6-azauridine as -D-ribonucleoside component have been prepared in a combinatorial (not parallel!) manner (see Formulae). All compounds have been characterized by elemental analyses, ESI mass spectrometry as well as by H-1-, and C-13-NMR, and UV spectroscopy. A selection of eight nucleolipids with different lipophilizing moieties, based on earlier findings, as well as of 5-fluorouridine as control were first tested on their cytotoxic effect towards PMA-differentiated human THP-1 macrophages. Those compounds which did not exhibit a significant inhibitory effect on the survival of the macrophages were next tested on their cytostatic/cytotoxic effect towards the human astrocytoma/oligodendroglioma GOS-3 cells as well as against the rat malignant neuroectodermal BT4Ca cell line. Additionally, induction of apoptosis of the cell lines was evaluated. It turned out that particularly a combined lipophilization of the nucleosides by an 2,3-O-ethyl levulinate residue plus a farnesyl moiety at N(3) of the pyrimidine moiety of the corresponding nucleolipids leads to an active compound with the highest probability. |
ISSN: | 16121872 | DOI: | 10.1002/cbdv.201500158 |
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