Lipophilic Pt(II) complexes with selective efficacy against cisplatin-resistant testicular cancer cells.

A series of dichloridoplatinum(II) complexes with selective and high cytotoxicity [IC(90)(96h)≤3 μM] against cisplatin-resistant 1411HP testicular cancer cells were identified. They bear stationary 6-aminomethylnicotinate or 2,4-diaminobutyrate ligands esterified with lipophilic terpenyl residues, i.e.

2-(4-(Tetrahydro-2H-pyran-2-yloxy)-undecyl)-propane-1,3-diamminedichloroplatinum(II): a novel platinum compound that overcomes cisplatin resistance and induces apoptosis by mechanisms different from that of cisplatin.

(4-(Tetrahydro-2H-pyran-2-yloxy)R1)R2-diamminedichloroplatinum(II) complexes (1-12) consisting of CDDP linked to THP via aliphatic CH2-spacers were tested in two TGCT cell lines. The most promising compound, 2-(4-(tetrahydro-2H-pyran-2-yloxy)-undecyl)-propane-1,3-diamminedichloroplatinum(II) (12), completely overcame CDDP resistance of 1411HP cells, correlating with increased and accelerated cellular platinum uptake and much faster initiation of apoptotic cell kill. At equitoxic IC90 concentrations, 12 induced accelerated DNA fragmentation and caspase -3 and PARP cleavages.

Monoterpenes as drug shuttles: cytotoxic (6-aminomethylnicotinate)dichloridoplatinum(II) complexes with potential to overcome cisplatin resistance.

(6-Aminomethylnicotinate)dichloridoplatinum(II) complexes 4 esterified with terpene alcohols were tested on a panel of five human tumor cell lines. While they were accumulated in all cell lines more readily than cisplatin (CDDP), their cytotoxicities were tumor-specific and structure-dependent. Cell lines known to feature elevated levels of antiapoptotic, ion-channel-affecting proteins or otherwise impaired caspase-9 activation responded better to 4 than to CDDP, e.

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.