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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 ASEP 0539762 Document Type J - Journal Article R&D Document Type Journal Article Subsidiary J Článek ve WOS Title Symmetric 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, RID
Carlos Morales, J. (ES)Number of authors 7 Article number 103786 Source Title Bioorganic Chemistry. - : Elsevier - ISSN 0045-2068
Roč. 99, jun 2020 (2020)Number of pages 18 s. Publication form Online - E Language eng - English Country US - United States Keywords gene-expression ; telomere ; sequence ; genome ; glycosides ; chemistry ; topology Subject RIV CE - Biochemistry OECD category Biochemistry and molecular biology R&D Projects EF15_003/0000477 GA MŠMT - Ministry of Education, Youth and Sports (MEYS) Method of publishing Limited access Institutional support BFU-R - RVO:68081707 UT WOS 000535442000003 EID SCOPUS 85082574275 DOI 10.1016/j.bioorg.2020.103786 Annotation Here 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. Workplace Institute of Biophysics Contact Jana Poláková, polakova@ibp.cz, Tel.: 541 517 244 Year of Publishing 2021 Electronic address https://www.sciencedirect.com/science/article/pii/S004520681931497X?via%3Dihub
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