Synthesis and characterization of thiocarbonato-linked platinum(IV) complexes

Herein we show the formation of new oxaliplatin-based platinum(tv) complexes by reaction with DSC-activated thiols via thiocarbonate linkage. Three model complexes based on aliphatic and aromatic thiols, as well as one complex with N-acetylcysteine as biologically active thiol were synthesized. This synthetic strategy affords the expansion of biologically active compounds other than those containing carboxylic, amine or hydroxy groups for coupling to the platinum(iv) center. The complexes were characterized by high-resolution mass spectrometry, NMR spectroscopy (H-1, C-13, Pt-195) and elemental analysis. Their biological behavior was evaluated against two ovarian carcinoma cell lines and their cisplatin-resistant analogues. Remarkably, the platinum(iv) samples show modest in vitro cytotoxicity against A2780 cells and comparable effects against A2780cis cells. Two complexes in particular demonstrate improved activity against SKOV3cis cells. The reduction experiment of complex 8, investigated by UHPLC-HRMS, provides evidence of interesting platinum-species formed during reaction with ascorbic acid.

Automated summary

Here, new oxaliplatin-based platinum(IV) complexes were synthesized through reaction with DSC-activated thiols via thiocarbonate linkage. This synthetic strategy expands the range of biologically active compounds and the cytotoxicity of these complexes was evaluated against various ovarian carcinoma cell lines.