期刊
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
卷 16, 期 6, 页码 1686-1691出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmcl.2005.12.019
关键词
demethylcantharidin; 1,2-diaminocyclohexane; anticancer agents; cell cycle
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.
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