Interaction of arylmethylene thiohydantoins with DNA

GUADALUPE FIRPO; WALTER J. PELÁEZ; MARTÍN S. FAILLACE; GUSTAVO A. ARGÜELLO; MAXI A. BURGOS PACI

Villa Carlos PAz

Encuentro; XIII ELAFOT; 2017

XIII ELAFOT

In many fields of chemistry and molecular biology, DNA detection is essential in order to study different phenomena. This can be achieved by dyes techniques employing fluorescent probes. The most commonly used dye is ethidium bromide (EtBr).[1] It is an intercalating agent which is also known for its toxicity and mutagenicity. So, the development of fluorescent probes capable to interact with DNA has attracted much attention.[2-3] Several ligands interact with DNA through covalent and electrostatic binding or intercalation. Compounds with rigid and planar structures are good candidates for DNA intercalation. In addition, some of these compounds are used in chemotherapeutic treatments to inhibit DNA replication in rapidly growing cells.[2]In this work, we synthetized thioxoimidazolidin-4-one derivatives (TH, 1a-c and 2a-c, figure 1), studied their luminescence properties and evaluated the possibility of their application in the detection of double stranded DNA (dsDNA). These compounds are good candidates as fluorescent probes due to their planar structure and the heteroatoms that may form hydrogen bonds. The fluorescent profile was examined in the absence and presence of fish dsDNA. Solutions of the samples were prepared in DMSO rising a final concentration of 0.3 mM. Ethidium bromide was analyzed at a lower concentration of 15µM due to its high fluorescence emission. All the analyses and incubation times were performed at a controlled temperature (30°C). The comparative results for the unsubstituted compounds (1a and 2a) are shown in figure 2 together with the spectrum for ethidium bromide at the concentration needed to reach similar emission intensities ([TH]/[EtBr]=20). Compound 1a presents a rather modest fluorescence emission which somewhat increases after incubation with dsDNA. In contrast, 2a, whose fluorescence emission is comparable to 1a, rises 20 times after 4 h of incubation with dsDNA. As it is possible to see, compound 2a interacts better with DNA because it has a bigger planar structure. In addition, compounds 1 present tautomerism which is a well-known mechanism of fluorescence deactivation. In spite of the higher concentration of the fused thiohydantoin derivatives compared to ethidium bromide (ratio of concentrations 20), we believe that the presenting compounds could perform as fluorescent probes because their emission appear well within the visible region besides of its reduced toxicity.