Platinum(II) complexes with l-methionylglycine and l-methionyl-l-leucine ligands: synthesis, characterization and in vitro antitumoral activity.
Four dipeptide complexes of the type [PtX(2)(dipeptide)] x H(2)O (X=Cl, I, dipeptide=l-methionylglycine, l-methionyl-l-leucine) were prepared. The complexes were characterized by (1)H, (13)C, (195)Pt NMR and infrared spectroscopy, DTG and elemental analysis. From the infrared, (1)H and (13)C NMR spectroscopy it was concluded that dipeptides coordinate bidentately via sulfur and amine nitrogen donor atoms. Confirmed with (13)C and (195)Pt NMR spectroscopy, each of the complexes exists in two diastereoisomeric forms, which are related by inversion of configuration at the sulfur atom. The (1)H NMR spectrum for the platinum(II) complex with l-methionylglycine and chloro ligands exhibited reversible, intramolecular inversion of configuration at the S atom; DeltaG( not equal)=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.
Kaluderović
Goran N
GN
Institut für Chemie, Martin-Luther-Universität Halle-Wittenberg, Kurt-Mothes-Strasse 2, D-06120 Halle, Germany. goran.kaluderovic@chemie.uni-halle.de
Schmidt
Harry
H
Paschke
Reinhard
R
Kalinowski
Bernd
B
Dietrich
Andrea
A
Mueller
Thomas
T
Steinborn
Dirk
D
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D004151:Dipeptides / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007930:Leucine / Q000737:chemistry* / Q000494:pharmacology; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000494:pharmacology*; D010984:Platinum / Q000737:chemistry* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004151:Dipeptides; D008024:Ligands; D009944:Organoplatinum Compounds; C098230:methionylglycine; D010984:Platinum; D007930:Leucine