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ISSN electronic edition: 1336-9075
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Bioactive papaverine derivatives bind G-quadruplexes selectively

Elzbieta Galezowska, Joanna Kosman, Agnieszka Stepien, Blazej Rubis, Maria Rybczynska, and Bernard Juskowiak

Faculty of Chemistry, Adam Mickiewicz University, Grunwaldzka 6, 60-780 Poznan, Poland



Abstract: G-quadruplexes are a family of DNA secondary structures resulting from the folding of a guanine-rich sequence. Targeting quadruplexes by small molecules is an approach that is currently being studied with the aim of exploring their biological roles and developing new anti-cancer agents. There is evidence that the formation of G4 structures by telomeric DNA can be used to inhibit the enzyme activity of telomerase, and thereby to activate the pathway to senescence in tumour cells. It was previously shown that the papaverine oxidation products 6a,12a-diazadibenzo-[a,g]fluorenylium derivative (ligand I) and 2,3,9,10-tetramethoxy-12-oxo-12H-indolo[2,1-a]isoquinolinium chloride (ligand II) bind to G-quadruplex representing the human telomeric sequence. These ligands possess the ability to inhibit telomerase and polymerase action at the micromolar level. Here we report a DNA binding study on these two ligands and a new derivative 2-(2-carboxy-4,5-dimethoxyphenyl0-6,7-dimethoxyisoquiloliniuminner salt (ligand III) in order to evaluate their binding selectivity to samples of nucleic acids (ssDNA, dsDNA, triplexes, and quadruplexes). Simultaneous investigations on several DNA-ligand complexes carried out using an equilibrium dialysis approach revealed pronounced binding selectivity of ligand I and ligand II to tetraplex DNA structures over the doublestranded DNA forms.

Keywords: DNA binding selectivity – equilibrium dialysis – fluorescence – G-quadruplex – papaverine derivatives – telomerase

Full paper is available at

DOI: 10.2478/s11696-011-0092-4


Chemical Papers 66 (2) 79–84 (2012)

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