Polycationic Monomeric and Homodimeric Asymmetric Monomethine Cyanine Dyes with Hydroxypropyl Functionality—Strong Affinity Nucleic Acids Binders

Abstract

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.

Selenium-Substituted Monomethine Cyanine Dyes as Selective G-Quadruplex Spectroscopic Probes with Theranostic Potential

“…Similar discrimination between ds-DNA and ds-RNA structures was shown by oxazole yellow homodimer (YOYO), whereas chlorinated TOTO (thiazole orange homodimer) demonstrated preferential binding to alternating DNA sequences compared to non-halogenated TOTO [11]. Furthermore, TO and TOTO with hydroxypropyl functionality could distinguish between GC-and AT-DNA by the binding affinity and the strong fluorescence signal [12]. Styryl dyes with N-Methylpiperazine and N-Phenylpiperazine functionalities demonstrated preferred binding to AT-DNA and G-quadruplex, respectively.…”

“…Alternating AT and GC polynucleotides were chosen as models for B-helix DNA and AU homopolynucleotide as a model for A-helical structure (RNA) [3,31,32]. As noted for most cyanine dyes [4,12,14], the addition of ds-DNA (AT-DNA, GC-DNA) or ds-RNA (AU-RNA) to solutions of compounds 1-6 led to an increase in their emission (see Figures S9-S26 in SI). Similarly, to recently reported styryl cyanine dyes [13], hypsochromic shifts (6-20 nm) were noticed in all titrations of 1-6 after adding aliquots of ds-DNA and ds-RNA.…”

Fluorescent Probes for Biomacromolecules Based on Monomethine Cyanine Dyes

“…The synthesis is performed via the reaction of a monomethine dye having an iodoalkyl group with tertiary diamine linkers. In [27], the synthesis of homodimeric derivatives of dye 1 (TO) with various linkers was described (Figure 8).…”

“…The high sensitivity and stability of the complexes of dimeric MCDs with nucleic acids explain the research interest in new compounds of this type. The study of the interaction of dimeric MCD 100-103 (Figure 26) with ds-polynucleotides and poly-rA-poly-rU showed the selectivity the of new dyes for GC base pairs compared to that of AT [27]. The presence of a positively charged linker results in a significant increase in the fluorescence intensity of the dyes upon binding to GC nucleotides (with AT, the increase is much lower).…”

The Benzothiazine Core as a Novel Motif for DNA-Binding Small Molecules

“…The information gathered through these kinds of investigations can be extremely useful for either drug design and optimization or the development of novel DNA/RNA probes. While benzothiazole-derived small molecules are commonly explored in medicinal chemistry [9] and investigated for their DNA-binding abilities [10,11], benzothiazine is a less researched scaffold, especially in the context of DNA binding despite the preferable photochemical properties of some of its derivatives. However, some benzothiazine derivatives have already been employed as sensors [12,13].…”