engleski

Halogenated thiazole orange dyes: synthesis, DNA/RNA binding and antiproliferative evaluations

Cyanine dyes were first synthesized over a century ago and since then found wide application in several fields. Originally, they were used in the development of photographic films, but they can also be used as luminescent markers of biomolecules or as sensitive probes for biomembrane fluidity.1, 2 Cyanine dyes are small organic molecules, which as free ligands exhibit inconsiderable or no fluorescence. However, when they interact with nucleic acids it leads to a significant increase in fluorescence.3 One of the most eminent examples of cyanine group is Thiazole Orange (TO) which consists of conjugated benzothiazole and quinoline aromatic rings. TO can intercalate between base pairs or bind inside the grooves of ds-DNA/RNA, which leads to increase in its fluorescence, making it a viable sensor probe for detection of nucleic acids in vitro as well as in vivo.4 Our intent was to evaluate the influence of three TO derivatives on recognition of various single-stranded, double-stranded, and triple- stranded DNA/RNA using several biophysical methods including thermal melting, fluorometry and circular dichroism. Confocal microscopy and MTT test were applied for in vitro study. All synthesized derivatives caused triplex formation of consecutive rA/dA-containing nucleic acid helices. In the case of derivative 3, the most pronounced effect was the induction of H-aggregate formation, which depended on the presence of rA strand in all forms of nucleic acids (single, double, and triple-stranded). Also, the same derivative stabilised all three triplex forms stronger than equivalent double- stranded forms. All TO derivatives exerted moderate to strong antiproliferative effect on all tumor cell lines. Compounds 2 and 3 were shown to be particularly good mitochondrial probes which, in addition to their demonstrated cytotoxic activity, makes them potential candidates for therapeutic agents.

Cyanine dyes ; rA/dA-containing nucleic acid helices ; Thiazole Orange ; fluorescence ; circular dichroism ; confocal microscopy ; MTT test

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