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RESEARCH PRODUCT
DNA-Binding and Anticancer Activity of Pyrene-Imidazolium Derivatives
Michelangelo GruttadauriaRiccardo BonsignoreGiuseppe FiasconaroBernhard K. KepplerBernhard K. KepplerMichela GiulianoAnna Maria Pia SalvoAntonietta NotaroGiampaolo BaroneFrancesco GiacaloneAngelo SpinelloAlessio TerenziAlessio Terenzisubject
Senescence010405 organic chemistryGeneral Chemistry010402 general chemistry01 natural sciences0104 chemical sciencesMolecular dynamicschemistry.chemical_compoundBreast cancer cell linechemistrySettore CHIM/03 - Chimica Generale E InorganicaBiophysicsPyreneCytotoxic T cellBiological activity · DNA · G-Quadruplexes · Molecular modelingDNAdescription
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.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2016-12-16 |