Serebryanskaya T.V.,Belarusian State University |
Yung T.,Saint Petersburg State University |
Bogdanov A.A.,Saint Petersburg State University |
Shchebet A.,University of Gottingen |
And 10 more authors.
Journal of Inorganic Biochemistry | Year: 2013
Two series of tetrazole-containing platinum(II) and palladium(II) chlorido complexes, trans-[ML2Cl2] (M = Pt, Pd) and cis-[PtL 2Cl2]·nH2O (n = 0, 1), where L is 1- or 2-substituted 5-aminotetrazole, have been synthesized and thoroughly characterized. Configuration of platinum(II) complexes obtained from the reaction of 5-aminotetrazoles with K2PtCl4 has been found to vary depending on the nature of tetrazole derivatives and reaction conditions. According to in vitro cytotoxic evaluation, only platinum complexes display noticeable antiproliferative effect, and their cytotoxicity depends strongly on their geometry and hydrophobicity of the carrier ligands. The most promising complexes are cis-[Pt(1-apt)2Cl2]·H 2O and cis-[Pt(2-abt)2Cl2]·H 2O, where 1-apt is 5-amino-1-phenyltetrazole and 2-abt is 5-amino-2-tert-butyltetrazole. In comparison with cisplatin, they show comparable cytotoxic potency against cisplatin-sensitive human cancer cell lines, cis-[Pt(2-abt)2Cl2]·H2O performing substantially higher activity against cisplatin-resistant cell lines. Cell cycle studies in H1299 cell line indicated that cis-[Pt(2-abt) 2Cl2]·H2O induced apoptosis launched from G2 accumulations. The DNA interaction with cis-[Pt(1-apt) 2Cl2]·H2O was followed by UV spectroscopy, circular dichroism, hydrodynamic and electrophoretic mobility studies. Both cis-[Pt(1-apt)2Cl2]·H2O and cis-[Pt(2-abt)2Cl2]·H2O complexes appeared to be significantly less toxic than cisplatin in mice, while only compound cis-[Pt(1-apt)2Cl2]·H2O displayed noticeable efficacy in vivo. © 2012 Elsevier Inc.