Synthesis, physicochemical and in vitro pharmacological investigation of new platinum (II) complexes with some cycloalkanespiro-5′-hydantoins

Platinum (II) complexes with cyclobutanespiro-5'-hydantoin and cycloheptanespiro-5'-hydantoin were synthesized and evaluated by means of general physicochemical methods. The data from the elemental analysis, IR and NMR spectra suggested the formation of cis-[Pt(C6H8N2O2)(2)(NH3)(2)](NO3)(2)center dot 4H(2)O (PtCBH), when cyclobutanespiro-5'-hydantoin was used as a ligand and cis-[Pt(C9H14N2O2)-(NH3)(2)](NO3)(2)center dot 4H(2)O (PtCHTH), when cycloheptanespiro-5'-hydantoin was used, respectively. The novel complexes exerted cytotoxic effects at micromolar concentrations against a panel of human tumor cell lines. They were found to trigger apoptosis in HL-60 and BV-173 cells as evidenced by DNA-laddering detection. The evaluation of the effects of PtCBH, PtCHTH and the antineoplastic drugs cisplatin and oxaliplatin against cultured murine kidney epithelial cells revealed that the hydantoin complexes were far less nephrotoxic in vitro. (c) 2005 Elsevier SAS. All rights reserved.