Palladium(II) complexes as possible chemotherapeutic agents: Synthesis, kinetics of reaction and in vitro screening

This work reports the synthesis and characterization of a series of palladium(II) analogues of cisplatin. The Pd(II) compounds are analogues composed of tridentate polypyridyl chelate ligands with one chloro ligand attached to the palladium metal. A similar binuclear compound previously synthesized was also used in the studies as a comparison for a binuclear compound versus a mononuclear one.

The kinetics of reaction of guanosine hydrate with [Pd(Terpy)Cl]Cl +, [Pd(BH)Cl]Cl+, [Pd(BMe)Cl]Cl +, [Pd(BEt)Cl]Cl+ and [Pd(BBu)Cl]Cl + were studied under pseudo-first-order conditions using stopped-flow spectrometry. The rate law for each compound was determined to be: Rate = kobs[Pd(ligand)Cl]+ = (k1 + k 2[Gu])[Pd]. From the temperature dependence of [Pd(Terpy)Cl]Cl +, [Pd(BH)Cl]Cl+and [Pd(BBu)Cl]Cl +, activation parameters were calculated using the Eyring equation.

The five substituted Pd(II) terpy compounds and the binuclear Pd(II) tppz compound were subjected to reaction with calf thymus DNA indicating a positive reaction.

Octanol-water partition coefficients were calculated for each of the Pd(II) compounds indicating a trend that supports active uptake by cellular membranes based on ligand structure.

The six Pd(II) compounds were subject to in vitro screening against human ovarian cancer (SKOV3), human breast cancer (MCF7) and human colon cancer (HT-29) cell lines. All six compounds presented significant cytotoxic effects towards all three cell lines. The significance is an increase in toxicity for [Pd(Terpy)Cl]Cl and [Pd(BBu)Cl]Cl.