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Two series of tetrazole-containing platinum(II) and palladium(II) chlorido complexes, trans-[ML(2)Cl(2)] (M=Pt, Pd) and cis-[PtL(2)Cl(2)]·nH(2)O (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 K(2)PtCl(4) 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)(2)Cl(2)]·H(2)O and cis-[Pt(2-abt)(2)Cl(2)]·H(2)O, 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)(2)Cl(2)]·H(2)O performing substantially higher activity against cisplatin-resistant cell lines. Cell cycle studies in H1299 cell line indicated that cis-[Pt(2-abt)(2)Cl(2)]·H(2)O induced apoptosis launched from G2 accumulations. The DNA interaction with cis-[Pt(1-apt)(2)Cl(2)]·H(2)O was followed by UV spectroscopy, circular dichroism, hydrodynamic and electrophoretic mobility studies. Both cis-[Pt(1-apt)(2)Cl(2)]·H(2)O and cis-[Pt(2-abt)(2)Cl(2)]·H(2)O complexes appeared to be significantly less toxic than cisplatin in mice, while only compound cis-[Pt(1-apt)(2)Cl(2)]·H(2)O displayed noticeable efficacy in vivo., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Hydrolytically stable PdII and PtII complexes supported by acyclic diaminocarbene ligands represent a novel class of structural organometallic anticancer agents exhibiting nanomolar antiproliferative activity in a panel of cancer cell lines (IC50 0.07–0.81 μM) and up to 300‐fold selectivity for cancer cells over normal primary fibroblasts. The lead drug candidate was 300 times more potent than cisplatin in vitro and showed higher efficacy in reducing the growth of aggressive MDA‐MB‐231 xenograft tumors in mice. [ABSTRACT FROM AUTHOR]

Abstract: Complexes CuL3Cl2, PdL2Cl2 and PtL2Cl2, where L is a novel ligand from the series of 2-substituted 5-aminotetrazoles, namely 5-amino-2-tert-butyltetrazole (1), have been synthesized by the reaction of metal(II) chlorides with 1 and characterized by IR spectroscopy, thermal and X-ray analyses. The crystallographic structural analysis of these complexes revealed that 1 acts as a monodentate ligand coordinated to the metal via endocyclic N4 atom. Platinum complex demonstrates promising cytotoxicity against human cervical carcinoma cells with IC50 value average between those of cisplatin and carboplatin. [Copyright &y& Elsevier]