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

0539762 - BFÚ 2021 RIV US eng J - Článek v odborném periodiku
Arevalo-Ruiz, M. - Amrane, M. - Rosu, F. - Belmonte-Reche, E. - Penalver, P. - Mergny, Jean-Louis - Carlos Morales, J.
Symmetric and dissymmetric carbohydrate-phenyl ditriazole derivatives as DNA G-quadruplex ligands: Synthesis, biophysical studies and antiproliferative activity.
Bioorganic Chemistry. Roč. 99, jun 2020 (2020), č. článku 103786. ISSN 0045-2068. E-ISSN 1090-2120
Grant CEP: GA MŠMT EF15_003/0000477
Institucionální podpora: RVO:68081707
Klíčová slova: gene-expression * telomere * sequence * genome * glycosides * chemistry * topology
Obor OECD: Biochemistry and molecular biology
Impakt faktor: 5.275, rok: 2020
Způsob publikování: Omezený přístup
https://www.sciencedirect.com/science/article/pii/S004520681931497X?via%3Dihub

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.
Trvalý link: http://hdl.handle.net/11104/0317459