Novel anticancer PdII complexes: The effect of the conjugation of transferrin binding peptide and the nature of halogen coordinated on antitumor activity

Abstract A series of Pd II complexes with bis-(2-pyridylmethyl)glycine as a ligand of formula [PdX(bis-(2-pyridylmethyl)glycine)] where X = Cl, Br, I were prepared and the effect of the halogen nature in the antitumor activity of eight tumorigenic and one non-tumorigenic cell line was evaluated. The chloride derivative was further functionalized with a transferrin receptor binding peptide, generating the first Pd II based metallopeptide. Its antitumor activity was also evaluated. However, among all the complexes, the chloride and iodine parent compounds showed the lowest GI 50 values in the panel evaluated, and lowest GI 50 than cisplatin in several cell lines. In contrast, the bromine derivative showed higher values of GI 50 than chloride and iodine (around 30–50 μM). The same trend was observed for the BSA binding constant with higher values for iodine, chlorine, and bromine in this order. In aqueous solution, the chloride is exchanged by water while the bromine and iodine are not. DNA was evaluated as a target and showed no significative interaction for all the compounds. The results suggest sulfur-rich proteins and not DNA as a target. This report represents the first Pd II metallopeptide reported, its evaluation in solution and antitumor activity. This work opens the possibilities for further functionalization of Pd II complexes and the importance of the halogen coordination in the design of novel metallodrugs.