title: Lipophilic Pt(II) complexes with selective efficacy against cisplatin-resistant testicular cancer cells.
abstract: 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., (-)/(+)-menthyl, (+)-cedrenyl, (-)-menthoxypropyl, or with a decyl-tethered 1,1,2-triphenylethene. They accumulated to a larger extent in 1411HP 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.
authors: Organic Chemistry Laboratory, University Bayreuth, Bayreuth, Germany.
authors: Bernhard
authors: B
authors: Biersack
authors: Andrea
authors: A
authors: Dietrich
authors: Miroslava
authors: M
authors: Zoldakova
authors: Bernd
authors: B
authors: Kalinowski
authors: Reinhard
authors: R
authors: Paschke
authors: Rainer
authors: R
authors: Schobert
authors: Thomas
authors: T
authors: Mueller
mesh_terms: D000111:Acetylcysteine / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry; D053938:DNA Fragmentation; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D004789:Enzyme Activation; D004996:Ethidium / Q000737:chemistry; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007364:Intercalating Agents / Q000737:chemistry; D008297:Male; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D010984:Platinum; D013736:Testicular Neoplasms
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D010984:Platinum; D004247:DNA; C505407:CASP3 protein, human; D053148:Caspase 3; D004996:Ethidium; D002945:Cisplatin; D000111:Acetylcysteine