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.

ARNA Laboratory INSERM U1212 CNRS UMR 5320 IECB University of Bordeaux F 33600 Pessac France; Institute of Biophysics AS CR v v i Kralovopolska 135 612 65 Brno Czech Republic; Laboratoire d'optique et Biosciences Ecole Polytechnique CNRS Inserm Institut Polytechnique de Paris Palaiseau France

Chemistry Department University of Burgos Pza Misael Bañuelos s n 09001 Burgos Spain

Molecular Biology Institute of Barcelona IBMB CSIC 08028 Barcelona Spain

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