Studies on the synthesis and activity of three tripalladium complexes containing planaramine ligands

The present study deals with the synthesis, characterization and activity against human cancer cell lines: A2780, A2780(cisR) and A2780(ZD0473R) of three tripalladium complexes, MH3, MH4 and MH5, that each have two planaramine ligands bound to the central metal ion. Cellular uptake levels, extent of DNA binding, and nature of interaction with salmon sperm and pBR322 plasmid DNA were determined for each complex. Palladium compounds are much more reactive than their corresponding platinum derivatives, which makes them therapeutically inactive but toxic. However, the results of the present study suggest that significant antitumour activity can be introduced in palladium complexes by lessening their reactivity by the introduction of sterically hindered ligands such as 2-hydroxypyridine, 3-hydroxypyridine and 4-hydroxypyridine. When bound to the central palladium ion, 4-hydroxypyridine appears to be more activating than 2-hydroxypyridine and 3-hydroxypyridine, suggesting that noncovalent interactions, such as hydrogen bonding, may also be key determinants of antitumour activity in addition to the steric effect. While cisplatin binds with DNA to form intrastrand GG adducts that causes local bending of a DNA strand, these planaramine-derived palladium complexes are expected to bind with DNA and form a number of long-range interstrand GG adducts that would cause a global change in DNA conformation, provided the tripalladium cations in MH3, MH4 and MH5 persist under physiological conditions.