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)]·4H2O (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)]·2DMF (5·2DMF; 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 μM (for 2), and 5.4 ± 3.8, and 3.6 ± 2.1 μM (for 5), respectively. The IC50 equals 9.2 ± 1.5 μM 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 μM and 19.6 ± 4.3 μM) and oxaliplatin (> 50.0 μM for both cancer cell lines).

[Pt(nL)2(ox)] – the first complexes involving a combination of adenine-based ligands (nL) and oxalate dianion (ox) coordinated to the Pt(II) ion – have been prepared using the reaction of K2[Pt(ox)2]·2H2O with 2-chloro-N6-(benzyl)-9-isopropyladenine or its benzyl-substituted analogues (nL). Prepared compounds have been fully characterized and tested on an MTT assay for their in vitro cytotoxicity against human osteosarcoma (HOS) and breast adenocarcinoma (MCF7) cancer cell lines. The in vitro cytotoxicity of some complexes exceeded that of well-known platinum-based anticancer drugs cisplatin and oxaliplatin.Figure optionsDownload as PowerPoint slide