RT info:eu-repo/semantics/article
T1 Influence of core extension and side chain nature in targeting G-quadruplex structures with perylene monoimide derivatives
A1 Busto Vázquez, Natalia
A1 García Calvo, José
A1 Cuevas Vicario, José Vicente
A1 Herrera, Antonio
A1 Mergny, Jean-Louis
A1 Pons, Sebastian
A1 Torroba Pérez, Tomás
A1 García Ruiz, Begoña
K1 G-quadruplexes
K1 Antiproliferative
K1 Perylenemonoimide
K1 DNA binding
K1 Química física
K1 Chemistry, Physical and theoretical
K1 Química orgánica
K1 Chemistry, Organic
K1 Química inorgánica
K1 Chemistry, Inorganic
AB 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.
PB Elsevier
SN 0045-2068
YR 2021
FD 2021-03
LK http://hdl.handle.net/10259/5677
UL http://hdl.handle.net/10259/5677
LA eng
NO “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.
DS Repositorio Institucional de la Universidad de Burgos
RD 04-dic-2024