Spectrophotometric study of DNA interactions with ftorafur and its elementoorganic derivatives

Ftorafur is an antimetabolite antitumour drug successfully used for treatment of various tumours. It is generally accepted that ftorafur is converted to 5-fluoruracil. However, some data indicate direct interactions of the compound with DNA. To test this hypothesis we have performed spectrophotometric study of DNA interactions of ftorafur and some of its elementoorganic derivatives with DNA. UV-VIS spectra of the tested compounds were recorded in absence and presence of increasing amounts of DNA. DNA caused a hypochromic effect in spectra of ftorafur, similar, but weaker effect was observed in 5-fluoruracil spectra. Trimethylgermyl derivative of ftorafur manifested a higher DNA-binding capacity compared to ftorafur. To reveal possible mechanism of interaction between the tested nucleosides and DNA ethidium bromide extrusion experiments were performed. It was shown that the compounds did not compete with EBr for intercalation. Fourier transformation infrared spectroscopy analyses revealed decrease in intensity of several bands in spectra of ftorafur, its trimethylgermyl derivative and fluorouracil in presence of DNA indicating again interactions between the compounds and DNA. Docking experiments reveal interactions of the tested nucleosides with the DNA minor groove. Thus ftorafur is capable to interact directly with DNA; further modifications of the molecule enhance this capacity.