Guanidiniocarbonylpyrrole-aryl derivatives: structure tuning for spectrophotometric recognition of specific DNA and RNA sequences and for antiproliferative activity

Chemistry : a European Journal
Laura Hernandez-FolgadoC Schmuck

Abstract

We present a systematic study of different guanidiniocarbonylpyrrole-aryl derivatives designed to interact with DNA or RNA both through intercalation of an aromatic moiety into the base stack of the nucleotide and through groove binding of a guanidiniocarbonylpyrrole cation. We varied 1) the size of the aromatic ring (benzene, naphthalene, pyrene and acridine), 2) the length and flexibility of the linker connecting the two binding groups, and 3) the total number of positive charges present at different pH values. The compounds and their interactions with DNA and RNA were studied by UV/Vis, fluorescence and CD spectroscopy. Antiproliferative activities against human tumour cell lines were also determined. Our studies show that efficient interaction with, for example, DNA requires a significantly large aromatic ring (pyrene) connected through a flexible linker to the pyrrole moiety. However, a positive charge, as in 12, is also needed. Compound 12 allows for base-pair-selective recognition of ds-DNA at physiological pH values. The antiproliferative activities of these compounds correlate with their binding affinities towards DNA, suggesting that their biological effects are most probably due to DNA binding.

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Citations

Dec 14, 2017·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Željka BanIvo Piantanida
Aug 7, 2010·Dalton Transactions : an International Journal of Inorganic Chemistry·Johan MattssonBruno Therrien
Mar 1, 2012·Chemistry : a European Journal·Lidija-Marija TumirIvo Piantanida
Apr 27, 2013·Chemphyschem : a European Journal of Chemical Physics and Physical Chemistry·Andreas T HaedlerHans-Werner Schmidt
Feb 18, 2012·Chemistry : a European Journal·Wenbin HuThomas Schrader
Apr 17, 2012·Dalton Transactions : an International Journal of Inorganic Chemistry·Mona Anca FurrerBruno Therrien
Oct 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Tamara ŠmidlehnerIvo Piantanida
Sep 29, 2020·Beilstein Journal of Organic Chemistry·Poulami JanaIvo Piantanida

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