SYNTHESIS, PHYSICO-CHEMICAL PROPERTIES AND CYTOTOXIC ACTIVITY OF BISCAROXYLATE COMPLEXES OF PLATINUM (II) WITH N-SUBSTITUTED 5-AMINOTETRAZOLES
Abstract
Effective methods for preparation of tetrazole-containing biscaroxylate complexes of platinum (II) were developed and novel oxalate, malonate and succinate platinum (II) complexes with 1-R- and 2-R-5-aminotetrazoles (R = 1-CH3, 2-CH3, 1-C6H5, 2-t-C4H9), analogues of third-generation antitumor platinum drugs were prepared. Studies of the obtained complexes showed their stability in solution, which is sufficient for biological studies. Cell proliferation tests and bioanalytical studies showed that increasing the hydrophobicity of substituents at the tetrazole heteroring leads to an increase in the intracellular concentration of complexes followed by a growth of their cytotoxic activity. Two platinum oxalate complexes with 5-amino-1-phenyl- and 5-amino-2-tert-butyltetrazoles having cis-configuration were chosen as leader compounds featuring the best combination of the antiproliferative activity, lipophilicity, and solubility.
About the Authors
T. V. SEREBRYANSKAYA
Научно-исследовательский институт физико-химических проблем БГУ, Минск
Belarus
Belarus
Y. V. GRIGORIEV
Научно-исследовательский институт физико-химических проблем БГУ, Минск
Belarus
Belarus
I. M. GRIGORIEVA
Научно-исследовательский институт физико-химических проблем БГУ, Минск
Belarus
Belarus
O. A. IVASHKEVICH
Belarus
References
1. Komeda S., Takayama H., Suzuki T. et al. // Metallomics. 2013. Vol. 5. P. 461–468.
2. Uemura M., Suzuki T., Nishio K. et al. // Metallomics. 2012. Vol. 4. P. 686–692.
3. Voitekhovich S. V., Serebryanskaya Т. V., Lyakhov A. S. et al. // Polyhedron. 2009. Vol. 28. P. 3614–3620.
4. Serebryanskaya T. V., Yung T., Bogdanov A. A. et al. // J. Inorg. Biochem. 2013. Vol. 120. P. 44–53.
5. Pasetto L. M., D’Andrea M. R., Brandes A. A. et al. // Critical Rev. Oncology/Hematology. 2006. Vol. 60. P. 59–75.
6. Scheffler H., You Y., Ott I. // Polyhedron. 2010. Vol. 29. P. 66–69.
7. Ott I., Scheffler H., Gust R. // Chem. Med. Chem. 2007. Vol. 2. P. 702–707.
8. Ronald A. H., William G. F. // J. Am. Chem. Soc. 1954. Vol. 76, N 3. P. 923–926.
9. Voitekhovich S. V., Gaponik P. N., Lyakhov A. S., Ivashkevich O. A. // Tetrahedron. 2008. Vol. 64. P. 8721–8725.
10. Vorobyov A. N., Gaponik P. N. Petrov P. T., Ivashkevich O. A. // Synthesis. 2006. P. 1307–1312.
11. Abramkin S. A., Jungwirth U., Valiahdi S. M. et al. // J. Med. Chem. 2010. Vol. 53. P. 7356–7364.
12. Liu W., Chen X., Ye Q. et al. // Inorg. Chem. 2011. Vol. 50. P. 5324–5326.
13. Štarha P., Trávníček Z., Popa I. // J. Inorg. Biochem. 2010. Vol. 104. P. 639–647.
14. Schäfer S., Ott I., Gust R., Sheldrick W. S. // Eur. J. Inorg. Chem. 2007. P. 3034–3046.
15. Knox R. J., Friedlos F., Lydall D. A., Roberts J. J. // Cancer Res. 1986. Vol. 46. P. 1972–1979.
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