Kowalczyk, Aleksandra and Piotrowicz, Michal and Gapinska, Magdalena and Trzybinski, Damian and Wozniak, Krzysztof and Golding, Taryn M. and Stringer, Tameryn and Smith, Gregory S. and Czerwieniec, Rafal and Kowalski, Konrad (2022) Chemistry of glycol nucleic acid (GNA): Synthesis, photophysical characterization and insight into the biological activity of phenanthrenyl GNA constituents. BIOORGANIC CHEMISTRY, 125: 105847. ISSN 0045-2068, 1090-2120
Full text not available from this repository. (Request a copy)Abstract
The knowledge pertaining to the chemistry and biological activity of glycol nucleic acid (GNA) components, like nucleosides and nucleotides, is still very limited. Herein we report on the preparation of the uracil nucleoside (1) and nucleotide ester GNA (2). The compounds are functionalised with a luminescent phenanthrenyl group. In DMSO, 1 and 2 are brightly fluorescent, with emission maxima at 390 nm, nanosecond decay times (0.6 and 0.75 ns, respectively), and quantum yields of ca. 0.2. In the solid phase, they show excimeric emission, with maxima at 495 nm (1) and 432 nm (2), and decay times of 3.7 ns (1) and 2.9 ns (2). The anticancer activity of the GNA components, as well as gemcitabine hydrochloride, used as a reference drug, were examined in vitro against human cancer HeLa and Ishikawa cells, as well as against normal L929 cells, using a battery of biochemical assays. Furthermore, biodistribution imaging studies were carried out in HeLa cells, with luminescence confocal microscopy, which showed that the compounds localized mainly in the lipophilic cellular compartments. Nucleoside (1) and nucleotide ester (2) features two different anticancer activity profiles. At 24 h of treatment, the nucleoside acts mainly as a toxin and induces necrosis in HeLa cells, whereas the nucleotide ester exhibits pro-apoptotic activity. At longer treatment times (72 h), the nucleoside and the reference, gemcitabine hydrochloride, featured almost identical signs of anticancer activity, such as S-phase cell cycle arrest, proliferation inhibition, and apoptosis induction. In view of this data, one can hypothesize that despite the structural differences, the newly obtained phenanthrenyl GNA nucleoside (1) and gemcitabine may share a common mechanism of anticancer activity in HeLa cancer cells. The GNA components were also examined as antiplasmodial agents against Plasmodium falciparum, in vitro. Nucleoside (1) was found to be more potent than nucleotide (2), displaying activity in the low micromolar range. Furthermore, both phenanthrene derivatives were found to display resistance indices at least 9-fold lower than chloroquine diphosphate (CQDP).
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DUPLEX STRUCTURE; NUCLEOSIDE; APOPTOSIS; CYTOTOXICITY; PRODUCT; ASSAYS; MTT; DNA; Phenanthrene; GNA; Luminescence; Anticancer; Antiplasmodial activity |
| Subjects: | 500 Science > 540 Chemistry & allied sciences |
| Divisions: | Chemistry and Pharmacy > Institut für Physikalische und Theoretische Chemie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Jan 2024 13:42 |
| Last Modified: | 31 Jan 2024 13:42 |
| URI: | https://pred.uni-regensburg.de/id/eprint/58387 |
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