Biopolym. Cell. 2005; 21(5):433-439.
http://dx.doi.org/10.7124/bc.000707
Bioorganic Chemistry
The N1-glycosilic analogues of 6-azacytidine. Cytotoxic effect and influence on transcription in vitro
1Palchikovs'ka L. G., 2Garmanchouk L. V., 1Alexeeva I. V., 1Usenko L. S., 1Shestakova T. S., 2Solyanik G. I., 1Shved A. D., 2Chekhun V. F.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. R. E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, NAS of Ukraine
    45, Vasilkivska Str., Kyiv, Ukraine, 01022

Abstract

Cytotoxic action of the series of synthesized 6-azacytidine glycoside analogues in the range of 10–2–10–6 M on the tumor cell lines of epithelial origin has been studied. The most essential cytotoxic effect of 6-azaC analogues has been found for the MCF-7 cell line of the breast cancer. 6-Azacytosine xylofuranoside is the most effective among the compounds investigated. Index IC50 for this compound is 0,63 ± 0,01 mM and it is 4–7 times less than IC50 for the other glycosides. The ability of analogues to modulate efficiency of model transcription system depending on the structure of glycosilyc fragment and concentration has been revealed.
Keywords: 6-aza cytidine, 6-azacytosine glycosides, cytotoxic effect, tumor cell lines, the modelling system of a transcription, T7 RNA polymerase
Full text: (PDF, in Ukrainian)

References

[1] Alexeeva I, Dyachenko N, Nosach L, Zhovnovataya V, Rybalko S, Lozitskaya R, Fedchuk A, Lozitsky V, Gridina T, Shalamay A, Palchikovskaja L, Povnitsa O. 6-azacytidine--compound with wide spectrum of antiviral activity. Nucleosides Nucleotides Nucleic Acids. 2001;20(4-7):1147-52.
[2] Abdullaeva MV, Frolov AF, Alexeeva IV, Palchykovskaja LI, Fedorova NE. Inhibitory effect of 6-azacytidine on human cytomegalovirus infection in cellular system. Biopolym Cell. 2004; 20(4):337-42.
[3] Nesterova NV, Dyachenko NS, Zagorodnaya SD, Baranova GV, Alexeeva IV, Palchikovskaya LI. Studying of anti Epstein-Barr virus activity of new nitrogen-containing heterocyclic compounds. Abstr. 18-th Int. Conf. on Antiviral Research (Barcelona, Spain, April 11—14, 2005). Antiviral Res. 2005; 65:A79.
[4] Alexeeva I, Palchikovskaya L, Shalamay A, Nosach L, Zhovnovataya V, Povnitsa O, Dyachenko N. 4-Amino-acid derivatives of 6-azacytidine: Structure-activity relationship. Acta Biochim Polon. 2000;47:95-101.
[5] Alexeeva IV, Palchikovskaya LI, Nosach LN, Usenko LS, Zhovnovataya VL, Dyachenko NS. The glycosilic analogues of 6-aza-cytidine: synthesis and antiviral activity. Biopolym Cell. 2004; 20(5):435-9.
[6] Petrusha NA. Anticancer properties of some anomalous nucleoside: Auth Thesis. ... kand. biol. nauk. Kiev, 1969; 15 p.
[7] Alexeeva IV, Palchikovs'ka LG, Usenko LS, Kostina VG. 5-Aminosubstituted triazine nucleosides and their furanidylic analogues: synthesis and primary screening on tumor cell models. Biopolym Cell. 2005; 21(2):174-9.
[8] Kostina VG, Alexeeva IV, Palchikovskaya LI. Synthesis of novel 2',3'-dideoxy-6-azacytidine derivatives – potential retroviral reproduction inhibitors. Biopolym. Cell. 2001; 17(6):560-4.
[9] Alley MC, Scudiero DA, Monks A, Hursey ML, Czerwinski MJ, Fine DL, Abbott BJ, Mayo JG, Shoemaker RH, Boyd MR. Feasibility of drug screening with panels of human tumor cell lines using a microculture tetrazolium assay. Cancer Res. 1988;48(3):589-601.
[10] Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983;65(1-2):55-63.
[11] Solyanik GI, Garmanchuk LV, Pyaskovskaya ON, Yakshibaeva YR, Gorbik GV. Sensitivity of Lewis lung carcinoma to cisplatin undergoes considerable variations during growth and metastasizing. Bull Exp Biol Med. 2004;138(3):295-7.
[12] Solyanik GI, Pyaskovskaya ON, Garmanchouk V. Cisplatin-resistant Lewis lung carcinoma cells possess increased level of VEGF secretion. Exp. Oncol. 2003;4:260—5.
[13] Puvvada MS, Forrow SA, Hartley JA, Stephenson P, Gibson I, Jenkins TC, Thurston DE. Inhibition of bacteriophage T7 RNA polymerase in vitro transcription by DNA-binding pyrrolo[2,1-c][1,4]benzodiazepines. Biochemistry. 1997;36(9):2478-84.
[14] Kukhanova M, Krayevsky A, Prusoff W, Cheng YC. Design of anti-HIV compounds: from nucleoside to nucleoside 5'-triphosphate analogs. Problems and perspectives. Curr Pharm Des. 2000;6(5):585-98. ttp://
[15] Robins RK, Finch RA, Avery TL. Nucleoside and nucleotide modulation of oncogenic expression. In: Anticancer drug discovery and development: natural products and new molecular models. Eds F. A. Valeriote, T. H. Corbett, L. H. Baker. Boston: Kluwer Acad, publ., 1994; 149-82.
[16] Preobrazhenskaya MN, Mel'nik SYA. Analog components of nucleic acids, nucleic acid metabolism inhibitors. Itogi nauki i tekhniki (Ser. Bioorg. khimiya; vol 1). M.: VINITI, 1984. 244 p.
[17] Tanaka J, Ishida T, Choi BI, Yasuda J, Watanabe T, Iwakura Y. Latent HIV-1 reactivation in transgenic mice requires cell cycle -dependent demethylation of CREB/ATF sites in the LTR. AIDS. 2003;17(2):167-75.