Monoterpenes as Drug Shuttles: Cytotoxic (6-Aminomethylnicotinate)dichloridoplatinum(II) Complexes with Potential To Overcome Cisplatin Resistance
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- 作者：Rainer Schobert ; Bernhard Biersack ; Andrea Dietrich ; Antje Grotemeier ; Thomas Mü ; ller ; Bernd Kalinowski ; Sebastian Knauer ; Wieland Voigt ; Reinhard Paschke
- 刊名：Journal of Medicinal Chemistry
- 出版年：2007
- 出版时间：March 22, 2007
- 年：2007
- 卷：50
- 期：6
- 页码：1288 - 1293
- 全文大小：263K
- 年卷期：v.50,no.6(March 22, 2007)
- ISSN：1520-4804
文摘
(6-Aminomethylnicotinate)dichloridoplatinum(II) complexes 4 esterified with terpene alcohols were testedon a panel of five human tumor cell lines. While they were accumulated in all cell lines more readily thancisplatin (CDDP), their cytotoxicities were tumor-specific and structure-dependent. Cell lines known tofeature elevated levels of antiapoptotic, ion-channel-affecting proteins or otherwise impaired caspase-9activation responded better to 4 than to CDDP, e.g., the HL-60 leukemia to the fenchyl and bornyl derivatives4a,b at an IC90 
10 
M. The (-)-menthyl complex 4g was far better accumulated and more efficacious inCDDP-resistant 1411HP male germ cell tumor cells than in the congenerous CDDP-sensitive H12.1 cellline. 4g also broke the CDDP resistance of 518A2 melanoma cells. Cell decay in each case was apoptoticas to TUNEL and Annexin V fluorescence assays. Some complexes 4 seem to positively modulate thepermeability of the cell membrane and of blocked mitochondrial anion channels.
10 M. The (-)-menthyl complex 4g was far better accumulated and more efficacious inCDDP-resistant 1411HP male germ cell tumor cells than in the congenerous CDDP-sensitive H12.1 cellline. 4g also broke the CDDP resistance of 518A2 melanoma cells. Cell decay in each case was apoptoticas to TUNEL and Annexin V fluorescence assays. Some complexes 4 seem to positively modulate thepermeability of the cell membrane and of blocked mitochondrial anion channels.