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Symmetric and dissymmetric carbohydrate-phenyl ditriazole derivatives as DNA G-quadruplex ligands: Synthesis, biophysical studies and antiproliferative activity

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    SYSNO ASEP0539762
    Document TypeJ - Journal Article
    R&D Document TypeJournal Article
    Subsidiary JČlánek ve WOS
    TitleSymmetric and dissymmetric carbohydrate-phenyl ditriazole derivatives as DNA G-quadruplex ligands: Synthesis, biophysical studies and antiproliferative activity
    Author(s) Arevalo-Ruiz, M. (ES)
    Amrane, M. (FR)
    Rosu, F. (FR)
    Belmonte-Reche, E. (ES)
    Penalver, P. (ES)
    Mergny, Jean-Louis (BFU-R) ORCID
    Carlos Morales, J. (ES)
    Number of authors7
    Article number103786
    Source TitleBioorganic Chemistry. - : Elsevier - ISSN 0045-2068
    Roč. 99, jun 2020 (2020)
    Number of pages18 s.
    Publication formOnline - E
    Languageeng - English
    CountryUS - United States
    Keywordsgene-expression ; telomere ; sequence ; genome ; glycosides ; chemistry ; topology
    Subject RIVCE - Biochemistry
    OBOR OECDBiochemistry and molecular biology
    R&D ProjectsEF15_003/0000477 GA MŠk - Ministry of Education, Youth and Sports (MEYS)
    Způsob publikováníOmezený přístup
    Institutional supportBFU-R - RVO:68081707
    UT WOS000535442000003
    EID SCOPUS85082574275
    DOI10.1016/j.bioorg.2020.103786
    AnnotationHere we present a novel G4-binding family of compounds based on a central core of phenyl ditriazole (PDTZ) modified with carbohydrates and phenyl pyrrolidinyl side-chains. Their synthesis was achieved using controlled click chemistry conditions to obtain both, symmetric and dissymmetric carb-PDTZ derivatives without any intermediate protecting steps through an optimized methodology. Binding of the new carb-PDTZ to a variety of G-quadruplex motifs was examined using different biophysical techniques. The symmetric carb-PDTZ derivatives were not able to stabilize G4, but the dissymmetric ones (containing one sugar and one phenyl pyrrolidinyl side-chain) did. Interestingly, the dissymmetric carb-PDTZ derivatives showed much higher G4 vs duplex DNA selectivity than the control compound PDTZ 1, which contains two phenyl pyrrodilinyl side-chains and no carbohydrates. Their potential antitumoral activity was also investigated by in vitro cytotoxicity measurements on different cancerous cell lines. All carb-PDTZ derivatives showed higher IC50 values than the control PDTZ 1, probably due to the lack of compound stability of some derivatives and to lower cellular uptake.
    WorkplaceInstitute of Biophysics
    ContactJana Poláková, polakova@ibp.cz, Tel.: 541 517 244
    Year of Publishing2021
    Electronic addresshttps://www.sciencedirect.com/science/article/pii/S004520681931497X?via%3Dihub
Number of the records: 1