Synthesis and anticancer activity of two highly water-soluble and ionic Pt(IV) complexes as prodrugs for Pt(II) anticancer drugs

Abstract Two new Pt(IV) complexes featuring mesylate as outer sphere anions, cis,trans,cis-[PtCl2(OH2)2 (NH3)2](CH3SO3)2 (SPt-1) and cis,trans,cis-[PtCl2(OH2)2((1R,2R-DACH)](CH3SO3)2 (SPt-2) were synthesized, and characterized by elemental analysis, 1H- and 13C-NMR,IR, and ESI-MS. Both complexes have excellent water-solubility and high molar conductivity as well as good water-stability. They exhibit an irreversible two-electron reduction event with the peak potentials (Ep) for the processes being − 0.39 V and − 0.64 V for SPt-1 and 0.09 V and − 0.52 V for SPt-2. The biological tests reveal that SPt-2 possesses high in vitro anticancer activity against three human cancer cell lines and its overall anticancer activity is slightly greater than that of oxaliplatin, whereas SPt-1 is less active than cisplatin. Moreover, the antitumor efficacy of SPt-2 on human colon carcinoma HCT-116 xenografts in nude mice is also greater than that of oxaliplatin, suggesting SPt-2 deserves further evaluation as a prodrug for oxaliplatin.