Nucleolipids of Canonical Purine ß-d-Ribo-Nucleosides: Synthesis and Cytostatic/Cytotoxic Activities Toward Human and Rat Glioblastoma Cells.
We report on the synthesis of two series of canonical purine ß-d-ribonucleoside nucleolipids derived from inosine and adenosine, which have been characterized by elemental analyses, electrospray ionization mass spectrometry (ESI MS) as well as by (1)H and (13)C NMR, and pH-dependent UV/Vis spectroscopy. A selection of the novel nucleolipids with different lipophilic moieties were first tested on their cytotoxic effect toward human macrophages. Compounds without a significant inhibitory effect on the viability of the macrophages were tested on their cytostatic/cytotoxic effect toward human astrocytoma/oligodendroglioma GOS-3 cells as well as against the rat malignant neuroectodermal BT4Ca cell line. In order to additionally investigate the potential molecular mechanisms involved in the cytotoxic effects of the derivatives on GOS-3 or BT4Ca cells, we evaluated the induction of apoptosis and observed the particular activity of the nucleolipid ethyl 3-{4-hydroxymethyl-2-methyl-6-[6-oxo-1-(3,7,11-trimethyl-dodeca-2,6,10-trienyl)-1,6-dihydro-purin-9-yl]-tetrahydro-furo[3,4-d][1,3]dioxol-2-yl}propionate (8 c) toward both human and rat glioblastoma cell lines in vitro.
Organic Chemistry I-Bioorganic Chemistry Institute of Chemistry of New Materials University of Osnabrück Barbarastr. 7 49069 Osnabrück Germany.
Christine
C
Knies
Anatomy and Cell Biology Department of Medical Cell Biology University of Marburg Robert-Koch-Straße 8 35032 Marburg Germany.
Katharina
K
Hammerbacher
Anatomy and Cell Biology Department of Medical Cell Biology University of Marburg Robert-Koch-Straße 8 35032 Marburg Germany.
Gabriel A
GA
Bonaterra
Anatomy and Cell Biology Department of Medical Cell Biology University of Marburg Robert-Koch-Straße 8 35032 Marburg Germany.
Ralf
R
Kinscherf
Organic Chemistry I-Bioorganic Chemistry Institute of Chemistry of New Materials University of Osnabrück Barbarastr. 7 49069 Osnabrück Germany.
Helmut
H
Rosemeyer
antitumor agents; cytotoxicity; glioblastomas; ketal lipophilicity; nucleolipids; prenylation