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

A series of dichloridoplatinum(II) complexes with selective and high cytotoxicity [IC90(96 h) <= 3 mu M] against cisplatin-resistant 1411 HP testicular cancer cells were identified. They bear stationary 6-aminomethylnicotinate or 2,4-diaminobutyrate ligands esterified with lipophilic terpenyl residues, i.e., (-)/(+)-menthyl, (+)-cedrenyl, (-)-menthoxypropyl, or with a decyl-tethered 1,1,2-triphenylethene. They accumulated to a larger extent in 1411 HP cells than in cells of the cisplatin-sensitive H12.1 germ cell tumour. Their mechanism of apoptosis induction differed from that of cisplatin by being independent of p53 and of caspase-3 activation and by an early loss of the mitochondrial membrane potential. The new complexes are promising candidates for the treatment of cisplatin-resistant testicular tumours. (C) 2011 Elsevier Inc. All rights reserved.