The data on surface enhanced IR absorption (SEIRA) of nucleic acids deposited on a metal substrate were obtained using FTIR in reflectance mode. A 200-400 A thick gold film on a glass plate was the metal substrate. The approximate enhancement factors of the SEIRA for different vibrations of nucleic acids in our experimental conditions were 3-5. The roughness of the Au surface was about 50 A. Application of this method to nucleic acids isolated from tumor cells revealed some possible peculiarities of their structural organization, namely, the appearance of unusual sugar and base conformations, modification of the phosphate backbone, redistribution of the H-bond net, and so forth. This method enhanced a set of the bands, which is impossible to observe in conventional IR geometry. The SEIRA spectra of the RNA from tumor cells showed more sensitivity to the grade of tumor malignancy than the spectra of the DNA. After application of the anticancer drug doxorubicin to sensitive and resistant strains, the DNA isolated from these strains had different spectral features, especially in the region of the phosphate I and II bands. As induced by anticancer drugs, the conformational changes in the DNA from resistant and sensitive cancer strains could be characterized with different levels of structure disordering.
We report on an improved method of synthesis of N-benzylaminoferrocene-based prodrugs and demonstrate its applicability by preparing nine new aminoferrocenes. Their effect on the viability of selected cancer cells having different p53 status was studied. The obtained data are in agreement with the hypothesis that the toxicity of aminoferrocenes is not dependent upon p53 status. Subsequently the toxicity of a selected prodrug (4) was investigated ex vivo using rat precision cut liver slices and in vivo on hybrid male mice BDF1. In both experiments no toxicity was observed: ex vivo, up to 10 μM; in vivo, up to 6 mg/kg. Finally, prodrug 4 was shown to extend the survival of BDF1 mice carrying L1210 leukemia from 13.7 ± 0.6 days to 17.5 ± 0.7 days when injected daily 6 times at a dose of 26 μg/kg starting from the second day after injection of L1210 cells.
The DNA from Carcinoma Guerina resistant and sensitive cells of Wistar line rats and their interaction with anti-cancer drugs--cis-platin and doxorubicin (DOX)--have been studied in in vivo experiments. Surface enhanced infrared absorption (SEIRA) in reflectance absorption spectroscopy (RAS) mode was applied for registration of conformational change of the DNA induced by cancer process and anti-cancer drugs. We have registered numerous minor changes in infrared spectra of the DNA from sensitive and resistant cells that could reflect essential changes in molecular structure of DNA from cancer cells. The most significant transformation was undergone by the sugar phosphate backbone of the DNA from cancer cells. The DNA from resistant cancer cells could be characterized as rigid structures and look like the canonical helix form of DNA being practically unchangeable after anti-cancer drug application. The structure of DNA from sensitive cancer cells seems to be flexible and after application of anti-cancer drugs drastically changes and approaches to structure of helix form. It has been shown that doxorubicin strongly influences the DNA structure, leading to DNA stabilization and formation of new H-bonds in DNA doxorubicin complex. We have registered slight cis-platin influence on the DNA structure in in vivo experiment. Principal component analysis of SEIRA spectra can select the DNA from cancer cells.
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