Trifunctionalized naphthalene diimides and dimeric analogues as g-quadruplex-targeting anticancer agents selected by affinity chromatography

Chiara Platella, Valentina Pirota, Domenica Musumeci, Federica Rizzi, Sara Iachettini, Pasquale Zizza, Annamaria Biroccio, Mauro Freccero, Daniela Montesarchio, Filippo Doria

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number1964
JournalInternational Journal of Molecular Sciences
Volume21
Issue number6
DOIs
Publication statusPublished - Mar 2020

Keywords

  • Anticancer drug
  • G-quadruplex
  • G-quadruplex-selective ligand
  • G4-CPG assay
  • Naphthalene diimide

ASJC Scopus subject areas

  • Catalysis
  • Molecular Biology
  • Spectroscopy
  • Computer Science Applications
  • Physical and Theoretical Chemistry
  • Organic Chemistry
  • Inorganic Chemistry

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