Pd(II) and Pt(II) Terpyridyl Complexes: Topoisomerase I Inhibition and Cytotoxicity

Abstract Pd(II) and Pt(II) terpyridyl complexes, [MCl(terpy-COOH)]Cl (M = Pd(1) or Pt(2); terpy-COOH = 2,2':6',2''-terpyridine-4'-carboxylic acid) were synthesized. The Pd(II) complex was rapidly hydrolyzed because a Pd(II) ion was active in ligand substitution, while hydrolysis of the Pt(II) complex was slow because of its inactivity. Their topoisomerase inhibitory activity was examined: the Pd complex showed higher activity than the Pt complex. The complexes also bound with ct-DNA: the binding constant of 1 was about twice larger than that of 2. The model studies suggested that the Pd complex coordinated faster with the His residue, to which topoisomerase bound phosphate ester than the Pt complex. The cytotoxicity against HeLa cells was evaluated by adding BSA: the Pd complex 1 was more cytotoxic than cisplatin, while no cytotoxicity was observed for the Pt complex 2. The binding constants of 2 with BSA were confirmed to be similar to 1. It is fascinating that the Pd complex, which has been conventionally considered low anticancer activity, shows higher cytotoxicity than the Pt complex with the same structure.