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oai: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

Busto Vázquez, Natalia García Calvo, José Cuevas Vicario, José Vicente Herrera, Antonio Mergny, Jean-Louis Pons, Sebastian Torroba Pérez, Tomás García Ruiz, Begoña 2021-04-05T11:46:16Z 2021-04-05T11:46:16Z 2021-03 0045-2068 http://hdl.handle.net/10259/5677 10.1016/j.bioorg.2021.104660 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. “la Caixa” Foundation (LCF/PR/PR12/11070003), Ministerio de Ciencia, Innovación y Universidades-FEDER (RTI2018-102040-B-100), Junta de Castilla y León-FEDER (BU305P18 and BU263P18) is gratefully acknowledged. N.B. is grateful to Aurore Guédin of the ARNA Laboratory for technical support and also to the financial support of the José Castillejo Program by the Spanish Ministry of Education, Culture and Sports (JC2015-00403). A.H. was funded by a Juan de la Cierva fellowship (FJCI-2015-26175) from the Ministerio de Economía y Competitividad. This research has made use of the high-performance computing resources of the Castilla y León Supercomputing Center (SCAYLE, https://www.scayle.es), financed by FEDER (Fondo Europeo de Desarrollo Regional). Networking support of NECTAR COST Action CA18202 is fully acknowledged. This work was supported by the SYMBIT project (reg. no. CZ.02.1.01/0.0/0.0/15_003/0000477) financed by the ERDF. application/pdf eng Elsevier 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 Attribution-NonCommercial-NoDerivatives 4.0 Internacional http://creativecommons.org/licenses/by-nc-nd/4.0/ info:eu-repo/semantics/openAccess G-quadruplexes Antiproliferative Perylenemonoimide DNA binding Química física Química orgánica Química inorgánica Chemistry, Physical and theoretical Chemistry, Organic Chemistry, Inorganic Influence of core extension and side chain nature in targeting G-quadruplex structures with perylene monoimide derivatives info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Bioorganic Chemistry 108 104660