TY - JOUR
T1 - Trifunctionalized naphthalene diimides and dimeric analogues as g-quadruplex-targeting anticancer agents selected by affinity chromatography
AU - Platella, Chiara
AU - Pirota, Valentina
AU - Musumeci, Domenica
AU - Rizzi, Federica
AU - Iachettini, Sara
AU - Zizza, Pasquale
AU - Biroccio, Annamaria
AU - Freccero, Mauro
AU - Montesarchio, Daniela
AU - Doria, Filippo
N1 - Funding Information:
Funding: The A.B. laboratory was funded by the Italian Association for Cancer Research (AIRC) (grant #21579).
Funding Information:
Acknowledgments: C.P. was supported by a FIRC-AIRC fellowship for Italy. S.I. and P.Z. were recipients of a fellowship from the Umberto Veronesi Foundation (FUV).
Publisher Copyright:
© 2020 by the authors. Licensee MDPI, Basel, Switzerland.
Copyright:
Copyright 2020 Elsevier B.V., All rights reserved.
PY - 2020/3
Y1 - 2020/3
N2 - A focused library of newly designed monomeric and dimeric naphthalene diimides (NDIs) was analyzed in its ability to recognize specific G-quadruplex (G4) structures discriminating duplex DNA. The best G4 ligands—according to an affinity chromatography-based screening method named G4-CPG—were tested on human cancer and healthy cells, inducing DNA damage at telomeres, and in parallel, showing selective antiproliferative activity on HeLa cancer cells with IC50 values in the low nanomolar range. CD and fluorescence spectroscopy studies allowed detailed investigation of the interaction in solution with different G4 and duplex DNA models of the most promising NDI of the series, as determined by combining the biophysical and biological assays’ data.
AB - A focused library of newly designed monomeric and dimeric naphthalene diimides (NDIs) was analyzed in its ability to recognize specific G-quadruplex (G4) structures discriminating duplex DNA. The best G4 ligands—according to an affinity chromatography-based screening method named G4-CPG—were tested on human cancer and healthy cells, inducing DNA damage at telomeres, and in parallel, showing selective antiproliferative activity on HeLa cancer cells with IC50 values in the low nanomolar range. CD and fluorescence spectroscopy studies allowed detailed investigation of the interaction in solution with different G4 and duplex DNA models of the most promising NDI of the series, as determined by combining the biophysical and biological assays’ data.
KW - Anticancer drug
KW - G-quadruplex
KW - G-quadruplex-selective ligand
KW - G4-CPG assay
KW - Naphthalene diimide
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U2 - 10.3390/ijms21061964
DO - 10.3390/ijms21061964
M3 - Article
C2 - 32183038
AN - SCOPUS:85081565146
VL - 21
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 6
M1 - 1964
ER -