engleski

Biological properties of cyanine dyes equipped with bulky phosphonium substituents

Small molecules targeting DNA/RNA have attracted significant scientific interest due to the medicinal, biochemical and biological implications of such molecular recognition events. To extend our recent investigations on the influence of the chemical structure to the fluorogenic properties of the dyes in presence of DNA, we herein report the biological properties of novel asymmetric monomeric monomethine cyanine dyes bearing oxazolopyridinium and quinolinium end groups and tributylphosphonium or triphenylphosphonium substituents in their molecules. Studied compounds efficiently bind into ds-DNA minor groove, exhibiting extraordinary increase of fluorescence (from zero emission of free compound to fluorescence of cca 500 a.u.). Cytotoxicity of tested compounds and doxorubicin, as a parallel control, was measured by MTT test on cell lines derived from solid tumours (MiaPaCa2, CaCo-2, HEp-2, HeLa, AGS, NCI-H358) and two normal cell lines (human-BJ and canine-MDCK). Obtained results show no effects on the cells growth at applied concentration range (0.1 – 0.0001 mM). Novel cyanine dyes suppressed cell growth from 15 to 30% at highest applied concentration (0.1 mM) what is negligible in comparison with doxorubicin effect and arrestment of cell growth up to 90% depending of the cell line. Uptake and intracellular distribution of two novel dyes in the living cells studied by fluorescence microscopy demonstrated efficient entering of compounds into the cells and accumulation in the nucleus mostly. The mechanism by which novel cyanines enter the living cells is unknown at present but due to their low molecular weight and hydrophobic properties well balanced with positive charge, diffusion through cell membrane could be proposed.

cyanine dyes; ds-DNA minor groove binders; MTT; doxorubicin; fluorescence

nije evidentirano