Trifunctionalized Naphthalene Diimides and Dimeric Analogues as G-Quadruplex-Targeting Anticancer Agents Selected by Affinity Chromatography.
Chiara PlatellaValentina PirotaDomenica MusumeciFederica RizziSara IachettiniPasquale ZizzaAnnamaria BiroccioMauro FrecceroDaniela MontesarchioFilippo DoriaPublished in: International journal of molecular sciences (2020)
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.
Keyphrases
- single molecule
- dna damage
- mass spectrometry
- cell cycle arrest
- high speed
- circulating tumor
- induced apoptosis
- tandem mass spectrometry
- high resolution
- cell free
- liquid chromatography
- endothelial cells
- capillary electrophoresis
- high performance liquid chromatography
- oxidative stress
- papillary thyroid
- cell death
- squamous cell
- high throughput
- electronic health record
- dna repair
- induced pluripotent stem cells
- molecular docking
- nucleic acid
- gene expression
- cancer therapy
- solid state
- pi k akt
- big data
- case control
- simultaneous determination
- machine learning
- squamous cell carcinoma
- data analysis
- energy transfer