Organic Chemistry Laboratory, University Bayreuth, Bayreuth, Germany.
J Inorg Biochem. 2011 Dec;105(12):1630-7. doi: 10.1016/j.jinorgbio.2011.08.028. Epub 2011 Sep 14.
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.
一系列具有选择性和高细胞毒性的二氯合铂(II)配合物[IC(90)(96h)≤3 μM]被鉴定为针对顺铂耐药的 1411HP 睾丸癌细胞。它们带有固定的 6-氨甲基烟酸盐或 2,4-二氨基丁酸酯配体，与亲脂性萜烯残基酯化，即(-)/(+)-薄荷基、(+)-雪松烯基、(-)-薄荷氧基丙基，或与带有癸基连接的 1,1,2-三苯乙烯。它们在 1411HP 细胞中的积累程度大于在顺铂敏感的 H12.1 生殖细胞瘤细胞中的积累程度。它们诱导细胞凋亡的机制与顺铂不同，不依赖于 p53 和 caspase-3 的激活，并且早期失去线粒体膜电位。这些新的配合物有望成为治疗顺铂耐药性睾丸肿瘤的候选药物。
