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 trans-planaramine-
palladium(II) complexes of the form trans-PdL(2)Cl(2), coded as EH1, 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 A2780(cisR) and A2780(ZD0473R) than against the parent cell line A2780. Among the three
palladium complexes, EH4 (which has the bulkiest carrier
ligand) 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 introduction of bulky
ligands can make them more active against
tumors.