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Chemistry of glycol nucleic acid (GNA): Synthesis, photophysical characterization and insight into the biological activity of phenanthrenyl GNA constituents

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cris.lastimport.scopus2024-02-12T19:57:25Z
dc.abstract.enThe 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)
dc.affiliationUniwersytet Warszawski
dc.contributor.authorKowalski, Konrad
dc.contributor.authorCzerwieniec, Rafał
dc.contributor.authorSmith, Gregory S.
dc.contributor.authorStringer, Tameryn
dc.contributor.authorGolding, Taryn M.
dc.contributor.authorWoźniak, Krzysztof
dc.contributor.authorTrzybiński, Damian
dc.contributor.authorGapińska, Magdalena
dc.contributor.authorPiotrowicz, Michał
dc.contributor.authorKowalczyk, Aleksandra
dc.date.accessioned2024-01-24T19:13:04Z
dc.date.available2024-01-24T19:13:04Z
dc.date.issued2022
dc.description.financeNie dotyczy
dc.description.volume125
dc.identifier.doi10.1016/J.BIOORG.2022.105847
dc.identifier.issn0045-2068
dc.identifier.urihttps://repozytorium.uw.edu.pl//handle/item/102982
dc.identifier.weblinkhttps://api.elsevier.com/content/article/PII:S0045206822002528?httpAccept=text/xml
dc.languageeng
dc.pbn.affiliationchemical sciences
dc.relation.ispartofBioorganic Chemistry
dc.relation.pages105847
dc.rightsClosedAccess
dc.sciencecloudnosend
dc.subject.enAnticancer
dc.subject.enAntiplasmodial activity
dc.subject.enGNA
dc.subject.enLuminescence
dc.subject.enPhenanthrene
dc.titleChemistry of glycol nucleic acid (GNA): Synthesis, photophysical characterization and insight into the biological activity of phenanthrenyl GNA constituents
dc.typeJournalArticle
dspace.entity.typePublication