Polycationic Monomeric and Homodimeric Asymmetric Monomethine Cyanine Dyes with Hydroxypropyl Functionality—Strong Affinity Nucleic Acids Binders
Ivana Mikulin,
Ivana Ljubić,
Ivo Piantanida,
Aleksey Vasilev,
Mihail Mondeshki,
Meglena Kandinska,
Lidija Uzelac,
Irena Martin-Kleiner,
Marijeta Kralj,
Lidija-Marija Tumir
Affiliations
Ivana Mikulin
Laboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb, Croatia
Ivana Ljubić
Laboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb, Croatia
Ivo Piantanida
Laboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb, Croatia
Aleksey Vasilev
Faculty of Chemistry and Pharmacy, Department of Pharmaceutical and Applied Organic Chemistry, Sofia University “St. Kliment Ohridski”, 1000 Sofia, Bulgaria
Mihail Mondeshki
Department of Chemistry, Johannes Gutenberg Universität Mainz, Duesbergweg 10–14, 55128 Mainz, Germany
Meglena Kandinska
Faculty of Chemistry and Pharmacy, Department of Pharmaceutical and Applied Organic Chemistry, Sofia University “St. Kliment Ohridski”, 1000 Sofia, Bulgaria
Lidija Uzelac
Laboratory of Experimental Therapy, Division of Molecular Medicine, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb, Croatia
Irena Martin-Kleiner
Laboratory of Experimental Therapy, Division of Molecular Medicine, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb, Croatia
Marijeta Kralj
Laboratory of Experimental Therapy, Division of Molecular Medicine, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb, Croatia
Lidija-Marija Tumir
Laboratory for Biomolecular Interactions and Spectroscopy, Division of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, P.O. Box 180, 10002 Zagreb, Croatia
New analogs of the commercial asymmetric monomethine cyanine dyes thiazole orange (TO) and thiazole orange homodimer (TOTO) with hydroxypropyl functionality were synthesized and their properties in the presence of different nucleic acids were studied. The novel compounds showed strong, micromolar and submicromolar affinities to all examined DNA ds-polynucleotides and poly rA–poly rU. The compounds studied showed selectivity towards GC-DNA base pairs over AT-DNA, which included both binding affinity and a strong fluorescence response. CD titrations showed aggregation along the polynucleotide with well-defined supramolecular chirality. The single dipyridinium-bridged dimer showed intercalation at low dye-DNA/RNA ratios. All new cyanine dyes showed potent micromolar antiproliferative activity against cancer cell lines, making them promising theranostic agents.
