Khokhar A R, Brown D B, McCormack J J, Hacker M P
Vermont Regional Cancer Center, University of Vermont, Burlington 05405.
Cancer Chemother Pharmacol. 1989;23(1):15-8. doi: 10.1007/BF00258451.
A series of aminoethylpyrrolidine-platinum complexes were synthesized and partially characterized for chemical structure. The leaving groups in this series of complexes were varied in an attempt to identify cytotoxic, water-soluble aminoethylpyrrolidine-platinum complexes. The cytotoxic activity was tested in vitro against L1210 cells sensitive to cis-diamminedichloroplatinum(II) (L1210/0), L1210 cells resistant to cis-diamminedichloroplatinum(II) (L1210/DDP), and L1210 cells resistant to 1,2-diaminocyclohexane platinum (L1210/DACH). The complexes were also tested for in vivo antitumor activity against L1210/0 cells injected i.p. The results of these studies indicate that the aminoethylpyrrolidine-platinum complexes have moderate antitumor activity but are cross-resistant in L1210/DDP cells. The degree of antitumor activity was dependent on the characteristic leaving group of a given complex.
合成了一系列氨乙基吡咯烷铂配合物，并对其化学结构进行了部分表征。该系列配合物中的离去基团各不相同，旨在鉴定具有细胞毒性的水溶性氨乙基吡咯烷铂配合物。针对对顺二氯二氨铂（II）敏感的L1210细胞（L1210/0）、对顺二氯二氨铂（II）耐药的L1210细胞（L1210/DDP）以及对1,2-二氨基环己烷铂耐药的L1210细胞（L1210/DACH），在体外测试了这些配合物的细胞毒性活性。还针对经腹腔注射的L1210/0细胞测试了这些配合物的体内抗肿瘤活性。这些研究结果表明，氨乙基吡咯烷铂配合物具有中等抗肿瘤活性，但在L1210/DDP细胞中存在交叉耐药性。抗肿瘤活性的程度取决于特定配合物的特征离去基团。
