Anticancer activity of a series of platinum complexes integrating demethylcantharidin with isomers of 1,2-diaminocyclohexane

被引:53
作者
Yu, CW
Li, KKW
Pang, SK
Au-Yeung, SCF
Ho, YP [1 ]
机构
[1] Chinese Univ Hong Kong, Sch Pharm, Shatin, Hong Kong, Peoples R China
[2] Chinese Univ Hong Kong, Dept Chem, Shatin, Hong Kong, Peoples R China
关键词
demethylcantharidin; 1,2-diaminocyclohexane; anticancer agents; cell cycle;
D O I
10.1016/j.bmcl.2005.12.019
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
A series of platinum complexes derived from integrating demethylcantharidin (DMC) with different isomers of 1,2-diaminocyclohexane (DACH) has been synthesized and found to exhibit superior in vitro anticancer activity against colorectal and human hepatocellular cancer cell lines when compared with oxaliplatin, cisplatin, and carboplatin. Flow cytometric analysis revealed that the trans-DACH-Pt DMC analogues showed similar behavior to oxaliplatin on affecting the cell cycle of the HCT116 colorectal cancer cell line, but distinct from that of cisplatin or carboplatin. The DACH component apparently dictates the trans-DACH-Pt-DMC complexes to behave mechanistically similar to oxaliplatin, whereas the DMC ligand appears to enhance the compounds' overall anticancer activity, probably by accelerating the cell cycle from G I to S-phase with subsequent onset of G2/M arrest and accompanying apoptosis. (C) 2005 Elsevier Ltd. All rights reserved.
引用
收藏
页码:1686 / 1691
页数:6
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