Synthesis and Cytotoxicity of Three trans-Palladium Complexes Containing Planaramine Ligands in Human Ovarian Tumor Models

摘要

The present study deals with the synthesis, characterization, and activity against human ovarian cancer cell lines A2780, A2780~(cisR), A2780~(ZD0473R), and SKOV-3 of three frans-planaramine-palladium(H) complexes of the form frans-PdL2Cl2, coded as EM, EH3, and EH4, for which L=2-methylpyridine, imidazole, and 1,2-α-imidazopyridine, respectively. The cellular accumulation of palladium, palladium-DNA binding levels, and the nature of interactions of the compounds with salmon sperm and pBR322 plasmid DNA were also determined. All three compounds were found to be less active than cisplatin, but unlike cisplatin they were found to be equally or more active against the resistant cell lines A278G~(cisR) and A2780~(ZD0473R) than against the parent cell line A2780. Among the three palladium complexes, EH4 {which has the bulkiest carrier tigand) was found to be most active, in line with the highest cellular accumulation of palladium and highest level of palladium-DNA binding resulting from the compound, EH4 was also found to cause the greatest conformational change to pBR322 plasmid DNA. The results of this study illustrate structure-activity relationships; in particular, they support the idea that the decreased reactivity of trans-palladium complexes through the introduc- tion of bulky ligands can make them more active against tumors.