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 the outer sphere anion, 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, high molar conductivity and good water stability. They exhibit an irreversible two-electron reduction event with the peak potentials (E_p) for the processes being −0.40 V for SPt-1 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 (HCT-116, A549 and MKN-1) 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 that SPt-2 deserves further evaluation as a prodrug for oxaliplatin.