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

A series of PdII 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 PdII based metallopeptide. Its antitumor activity was also evaluated. However, among all the complexes, the chloride and iodine parent compounds showed the lowest GI50 values in the panel evaluated, and lowest GI50 than cisplatin in several cell lines. In contrast, the bromine derivative showed higher values of GI50 than chloride and iodine (around 30 – 50 μM). The same trend was observed for the bovine serum albumin 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 PdII metallopeptide reported, its evaluation in solution and antitumor activity. This work opens the possibilities for further functionalization of PdII complexes and the importance of the halogen coordination in the design of novel metallodrugs. New PdII complex conjugated with transferrin binding peptide obtained by solid phase conjugation. The effect of the halogen demonstrated iodine improves cytotoxicity and selectivity. [Display omitted] •A novel PdII complex conjugated to a transferrin binding peptide was characterized.•A novel series of PdII complexes with bpg and different halogen ligands were studied.•Selective activity for leukemia cells was found for the iodine derivative.•The chloride derivative was active in low μM range in all cell lines.•The bromine derivative was not active.