Abstract
The relationship between the lipophilicity, cytotoxic effects, and intracellular accumulation for potential antitumor agents, viz., amino complexes of platinum(IV) with the redox-active nitroxyl radicals cis,trans,cis-PtIV(RNH2)(NH3)(OCOR´)2Cl2 (R is 2,2,6,6-tetramethyl-1-oxylpiperidin-4-yl, OCOR´ are n-alkylcarboxylates C2—C8), was studied in comparison with cisplatin. In a series of four platinum nitroxyl complexes (PNCs), an increase in the lipophilicity was found to lead to a considerable increase in the cytotoxicity and the efficiency of accumulation in HeLa cells. However, PNCs are characterized by the slower development of cytotoxic effects after a short time exposure compared with hydrophilic cisplatin. This can be attributed to the fact that PtIV complexes are prodrugs and need to be reduced to chemically more active PtII derivatives in order to exhibit cytotoxic effects.
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N. J. Wheate, S. Walker, G. E. Craig, R. Oun, J. Chem. Soc., Dalton Trans., 2010, 39, 8113.
Martindale: The Complete Drug Reference, Ed. S. C. Sweetman, Pharmaceutical Press, London, 2007, 3322 p.
B. Koeberle, M. T. Tomicic, S. Usanova, B. Kaina, Biochim. Biophys. Acta, 2010, 1806, 172.
F.-S. Liu, Taiwan, J. Obstet. Gynecol., 2009, 48, 239.
M. M. K. Shahzad, G. Lopez-Berestein, A. K. Sood, Drug Resist. Updat., 2009, 12, 148.
V. D. Sen′, A. A. Terentiev, N. P. Konovalova, Nitroxides — Theory, Experiment and Applications, Ed. A. I. Kokorin, InTech, Croatia, 2012, 385.
M. B. Gariboldi, S. Lucchi, C. Caserini, R. Supino, C. Oliva, E. Monti, Free Rad. Biol. Med., 1998, 24, 913.
M. B. Gariboldi, V. Rimoldi, R. Supino, E. Favini, E. Monti, Free Rad. Biol. Med., 2000, 29, 633.
M. B. Gariboldi, R. Ravizza, C. Petterino, M. Castagnaro, G. Finocchiaro, E. Monti, Eur. J. Cancer, 2003, 39, 829.
S. Suy, J. B. Mitchell, A. Samuni, S. Mueller, U. Kasid, Cancer, 2005, 103, 1302.
S. M. Hahn, Z. Tochner, C. M. Krishna, J. Glass, L. Wilson, A. Samuni, M. Sprague, D. Venzon, E. Glatstein, J. B. Mitchell, Cancer Res., 1992, 52, 1750.
N. M. Emanuel, N. P. Konovalova, in Bioactive Spin Labels, Ed. R. I. Zhdanov, Springer-Verlag, N.-Y, 1992, 439.
V. D. Sen, V. A. Golubev, N. Yu. Lugovskaya, T. E. Sashenkova, N. P. Konovalova, Russ. Chem. Bull. (Int. Ed.), 2006, 55, 62 [Izv. Akad. Nauk, Ser. Khim., 2006, 60].
N. V. Komleva, G. V. Kostyuk, I. I. Parkhomenko, I. V. Balalaeva, V. A. Golubev, V. D. Sen′, A. A. Terent′ev, Vestn. NNGU im. Lobachevskogo [Bull. N. I. Lobachevsky Nizhny Novgorod State Univ.], 2011, No. 2, 82 (in Russian).
T. Mosmann, J. Immunol. Methods, 1983, 65, 55.
F. Denizot, R. Lang, J. Immunol. Methods, 1986, 89, 271.
J. Carmichael, W. G. DeGraff, A. F. Gazdar, J. D. Minna, J. B. Mitchell, Cancer Res., 1987, 47, 936.
C. V. Eadsforth, P. Moser, Chemosphere, 1983, 12, 1459.
O. H. Lowry, N. J. Rosebrough, A. L. Farr, R. J. Randall, J. Biol. Chem., 1951, 193, 265.
M. S. Clegg, C. L. Keen, B. Lönnerdal, L. S. Hurley, Biol. Trace Elem. Res., 1981, 3, 107.
K. M. Watling, J. F. Parr, L. Rintoul, C. L. Brown, L. A. Sullivan, Spectrochim. Acta, Part A, Mol. Biomol. Spectrosc., 2011, 80, 106.
T. Talarico, D. R. Phillips, G. B. Deacon, S. Rainone, L. K. Webster, Invest. New Drugs, 1999, 17, 1.
S. Dhar, S. J. Lippard, in Platinum and Other Heavy Metal Compounds in Cancer Chemotherapy. Cancer Drug Discovery and Development, Eds A. Bonetti, R. Leone, F. Muggia, S. B. Howell, Humana Press, 2009, 135.
V. D. Sen′, A. V. Shugalii, A. V. Kulikov, Russ. Chem. Bull. (Int. Ed.), 2002, 51, 1058 [Izv. Akad. Nauk, Ser. Khim., 2002, 972].
D. Screnci, M. J. McKeage, P. Galettis, T. W. Hambley, B. D. Palmer, B. C. Baguley, Br. J. Cancer, 2000, 82, 966.
A. M. Samuni, Y. Barenholz, Free Rad. Biol. Med., 2003, 34, 177.
A. V. Shugalii, A. V. Kulikov, M. V. Lichina, V. A. Golubev, V. D. Sen′, J. Inorg. Biochem., 1998, 69, 67.
J. L. Carr, M. D. Tingle, M. J. McKeage, Cancer Chemother. Pharmacol., 2002, 50, 9.
P. Gramatica, E. Papa, M. Luini, E. Monti, M. B. Gariboldi, M. Ravera, D. Osella, J. Biol. Inorg. Chem., 2010, 15, 1157.
G. T. Wondrak, Antioxid. Redox Signal., 2009, 11, 3013.
V. D. Sen´, N. A. Rukina, V. V. Tkachev, A. V. Pis´menskii, L. M. Volkova, S. A. Goncharova, T. A. Raevskaya, A. G. Tikhomirov, L. B. Gorbacheva, N. P. Konovalova, Russ. Chem. Bull. (Int. Ed.), 2000, 49, 1613 [Izv. Akad. Nauk, Ser. Khim., 2000, 1624].
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On the occasion of the 100th anniversary of the birth of Academician N. K. Kochetkov (1915—2005).
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 5, pp. 1178—1182, May, 2015.
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Komleva, N.V., Lapshina, M.A., Kostyuk, G.V. et al. Comparative analysis of cytotoxic effects and intracellular accumulation of platinum(IV) nitroxyl complexes. Russ Chem Bull 64, 1178–1182 (2015). https://doi.org/10.1007/s11172-015-0996-1
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DOI: https://doi.org/10.1007/s11172-015-0996-1