Preparation of antitumor oxaliplatin/cisplatin docking dinuclear platinum complex

A new dinuclear docking Pt(II) complex, (cis-diammine) (l-1,2-cyclohexanediamine)(μ-dichloro)-diplatinum(II) oxalate was synthesized by reacting oxaliplatin(l-OHP, [Pt(oxalato)(l-dach)]), l-dach = 1R, 2R-cyclohexanediamine), with cisplatin (CDDP). Elemental analysis of the compound indicated that it was 1:1 molar ratio complex of oxaliplatin and cisplatin. A plausible chemical structure has been proposed as Cl– bridged dinuclear complex, judged from its yellow coloration and NMR spectral analysis. This complex can be denoted as, i.e. [Pt2Cl2(NH3)2(l-dach)](COO)2 (l-OHP/CDDP). The complex showed higher cytotoxicity against L1210 than the parent complexes and low cross-resistance against L1210/CDDP and L1210/DACH. Its antitumor activity was also tested in vivo against murine leukemia L1210 cell lines. The complex showed much higher activity than the mixture(1:1 molar ratio) of oxaliplatin and cisplatin. The antitumor effect against L1210/CDDP was very high, showing collateral sensitivity, being similar to that of oxaliplatin, and against L1210/DACH it showed no cross-resistance.