2024-03-28T17:32:30Zhttps://riubu.ubu.es/oai/requestoai:riubu.ubu.es:10259/56772022-11-21T12:04:43Zcom_10259_4354com_10259_5086com_10259_2604com_10259_4363com_10259_4365col_10259_4355col_10259_4364col_10259_4366
Influence of core extension and side chain nature in targeting G-quadruplex structures with perylene monoimide derivatives
Busto Vázquez, Natalia
García Calvo, José
Cuevas Vicario, José Vicente
Herrera, Antonio
Mergny, Jean-Louis
Pons, Sebastian
Torroba Pérez, Tomás
García Ruiz, Begoña
G-quadruplexes
Antiproliferative
Perylenemonoimide
DNA binding
A structure–activity relationship (SAR) study in terms of G-quadruplex binding ability and antiproliferative activity of six fluorescent perylenemonoimide (PMIs) derivatives is reported. A positive charge seems to be the key to target G4. This study also reveals the importance of the element substitution in the potential biological activity of PMIs, being the polyethylene glycol (PEG) chains in the peri position responsible for their antiproliferative activity. Among them, the cationic PMI6 with two PEG chains is the most promising compound since its fluorescence is enhanced in the presence of G-quadruplex structures. Moreover, PMI6 binds to the human telomeric G-quadruplex hTelo with high affinity and displays a high antiproliferative potential towards HeLa (cervical adenocarcinoma), A549 (lung adenocarcinoma) and A2780 (ovarian adenocarcinoma) cells. Its fate can be followed inside cells thanks to its fluorescent properties: the compound is found to accumulate in the mitochondria.
2021-04-05T11:46:16Z
2021-04-05T11:46:16Z
2021-03
info:eu-repo/semantics/article
0045-2068
http://hdl.handle.net/10259/5677
10.1016/j.bioorg.2021.104660
eng
Bioorganic Chemistry. 2021, V. 108, 104660
https://doi.org/10.1016/j.bioorg.2021.104660
info:eu-repo/grantAgreement/FundaciónLaCaixa/LCF/PR/PR12/11070003
info:eu-repo/grantAgreement/MICINN/RTI2018-102040-B-100
info:eu-repo/grantAgreement/JCyL/BU305P18
info:eu-repo/grantAgreement/JCyL/BU263P18
http://creativecommons.org/licenses/by-nc-nd/4.0/
info:eu-repo/semantics/openAccess
Attribution-NonCommercial-NoDerivatives 4.0 Internacional
Elsevier