DNA-Binding and Anticancer Activity of Pyrene-Imidazolium Derivatives
- Author(s)
- Riccardo Bonsignore, Antonietta Notaro, Anna Maria Pia Salvo, Angelo Spinello, Giuseppe Fiasconaro, Alessio Terenzi, Francesco Giacalone, Bernhard Keppler, Michela Giuliano, Michelangelo Gruttadauria, Giampaolo Barone
- Abstract
DNA-binding investigations showed that two different derivatives endowed with pyrene and imidazolium moieties, 1 and 2, strongly bind both double-stranded DNA and telomeric sequences in G-quadruplex (G4) conformation. The values of the DNA-binding constants indicate that 1 and 2 show preferential affinity for G4-DNA, of about one and two orders of magnitude, respectively. Moreover, 1 and 2 inhibit short and long-term proliferation of breast cancer cell lines in a time- and dose-dependent fashion. Remarkably, senescence assays indicate that telomeric G4-DNA is a possible biotarget for the cytotoxic activity of 2. Molecular dynamics simulations suggest that the stronger binding of 2 with G4-DNA and the related senescence induction, are a consequence of additional edge-to-face interactions with a base in the TTA loop.
- Organisation(s)
- Department of Inorganic Chemistry
- External organisation(s)
- Università degli Studi di Palermo
- Journal
- Chemistry SELECT
- Volume
- 1
- Pages
- 6755–6761
- No. of pages
- 7
- ISSN
- 2365-6549
- DOI
- https://doi.org/10.1002/slct.201601502
- Publication date
- 12-2016
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 104003 Inorganic chemistry, 301904 Cancer research, 106002 Biochemistry
- Keywords
- ASJC Scopus subject areas
- General Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/114f6c97-c683-4e4c-8dde-f04b9f48a234