Platinum(II) complexes with l-methionylglycine and l-methionyl-l-leucine ligands: Synthesis, characterization and in vitro antitumoral activity

Abstract

Four dipeptide complexes of the type [PtX2(dipeptide)] · H2O (X = Cl, I, dipeptide = l-methionylglycine, l-methionyl-l-leucine) were prepared. The complexes were characterized by 1H, 13C, 195Pt NMR and infrared spectroscopy, DTG and elemental analysis. From the infrared, 1H and 13C NMR spectroscopy it was concluded that dipeptides coordinate bidentately via sulfur and amine nitrogen donor atoms. Confirmed with 13C and 195Pt NMR spectroscopy, each of the complexes exists in two diastereoisomeric forms, which are related by inversion of configuration at the sulfur atom. The 1H NMR spectrum for the platinum(II) complex with l-methionylglycine and chloro ligands exhibited reversible, intramolecular inversion of configuration at the S atom; ΔG≠ = 72 kJ mol−1 at coalescence temperature 349 K was calculated. In vitro cytotoxicity studies using the human tumor cell lines liposarcoma, lung carcinoma A549 and melanoma 518A2 revealed considerable activity of the platinum(II) complex with l-methionylglycine and chloro ligands. Further in vitro cytotoxic evaluation using human testicular germ cell tumor cell lines 1411HP and H12.1 and colon carcinoma cell line DLD-1 showed moderate cytotoxic activity for all platinum(II) complexes only in the cisplatin-sensitive cell line H12.1. Platinum uptake studies using atomic absorption spectroscopy indicated no relationship between uptake and activity. Potential antitumoral activity of this class of platinum(II) complexes is dependent on the kind of ligands as well as on tumor cell type.