Platinum(II) oxalato complexes with adenine-based carrier ligands showing significant in vitro antitumor activity

[Pt(L)(2)(ox)] (1), [Pt(2-OMeL)(2)(ox)] (2), [Pt(3-OMeL)(2)(ox)] (3), [Pt(2,3-diOMeL)(2)(ox)] (4), [Pt(2,4-diOMeL)(2)(ox)] (5), [Pt(3,4-diOMeL)(2)(ox)] (6) and [Pt(3,5-diOMeL)(2)(ox)]center dot 4H(2)O (7) platinum(II) oxalato (ox) complexes were synthesized using the reaction of potassium bis(oxalato)platinate(II) dihydrate with 2-chloro-N6-(benzyl)-9-isopropyladenine or its benzyl-substituted analogues (nL). The complexes 1-7, which represent the first platinum(II) oxalato complexes involving adenine-based ligands, were fully characterized by various physical methods including multinuclear and two dimensional NMR spectroscopy. A single-crystal X-ray analysis of [Pt(2,4-diOMeL)(2)(ox)]center dot 2DMF (5 center dot 2DMF; DMF=N,N'-dimethylformamide), proved the slightly distorted square-planar geometry in the vicinity of the Pt(II) ion with one bidentate-coordinated oxalate dianion and two adenine derivatives (nL) coordinated to the Pt(II) centre through the N7 atom of an adenine moiety, thereby giving a PtN2O2 donor set. In vitro cytotoxicity of the prepared complexes was tested by an MTT assay against osteosarcoma (HOS) and breast adenocarcinoma (MCF7) human cancer cell lines. The best results were achieved for the complexes 2 and 5 in the case of both cell lines, whose IC50 values equalled 3.6 +/- 1.0, and 4.3 +/- 2.1 mu M (for 2), and 5.4 +/- 3.8, and 3.6 +/- 2.1 mu M (for 5), respectively. The IC50 equals 9.2 +/- 1.5 mu M against MCF7 cells in the case of 1. The in vitro cytotoxicity of the mentioned complexes significantly exceeded commercially used platinum-based anticancer drugs cisplatin (34.2 +/- 6.4 mu M and 19.6 +/- 4.3 mu M) and oxaliplatin (>50.0 mu M for both cancer cell lines). (C) 2010 Elsevier Inc. All rights reserved.