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Novel Nucleolipids of Pyrimidine β ‐ D ‐Ribonucleosides: Combinatorial Synthesis, Spectroscopic Characterization, and Cytostatic/Cytotoxic Activities
Author(s) -
Knies Christine,
Hammerbacher Katharina,
Bonaterra Gabriel A.,
Kinscherf Ralf,
Rosemeyer Helmut
Publication year - 2016
Publication title -
chemistry and biodiversity
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.427
H-Index - 70
eISSN - 1612-1880
pISSN - 1612-1872
DOI - 10.1002/cbdv.201500158
Subject(s) - chemistry , pyrimidine , moiety , ribonucleoside , cytotoxic t cell , stereochemistry , uridine , cell culture , in vitro , biochemistry , rna , genetics , biology , gene
Abstract Four series of nucleolipids with either uridine, 5‐methyluridine, 5‐fluorouridine, and 6‐azauridine as β ‐ 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 1 H‐, and 13 C‐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.