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.

Bonsignore, 1., Notaro, A., Salvo, A., Spinello, A., Fiasconaro, G., Terenzi, A., et al. (2016). DNA-Binding and Anticancer Activity of Pyrene-Imidazolium Derivatives. CHEMISTRYSELECT, 1(1), 6755-6761 [10.1002/slct.201601502].

DNA-Binding and Anticancer Activity of Pyrene-Imidazolium Derivatives

Bonsignore, Riccardo;NOTARO, Antonietta;SALVO, Anna Maria Pia;SPINELLO, Angelo;TERENZI, Alessio;GIACALONE, Francesco;GIULIANO, Michela;GRUTTADAURIA, Michelangelo;BARONE, Giampaolo
2016-01-01

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.
2016
Settore CHIM/03 - Chimica Generale E Inorganica
Bonsignore, 1., Notaro, A., Salvo, A., Spinello, A., Fiasconaro, G., Terenzi, A., et al. (2016). DNA-Binding and Anticancer Activity of Pyrene-Imidazolium Derivatives. CHEMISTRYSELECT, 1(1), 6755-6761 [10.1002/slct.201601502].
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10447/222903
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