Recent Advances Involving Palladium (II) Complexes for the Cancer Therapy

Antonio   Carlos Favero   Caires

doi:10.2174/187152007781668661

Abstract

This review deals with the most important results published on the structures, reactivity and biomedical applications of palladium( II) complexes in the cancer therapy in the last five years. Biological mechanisms of palladium(II) complexes, especially of palladacycle compounds were boarded. Among the most recent advances in the studies involving correlations between chemical structures of palladacycle compounds and biological activities we mention i) the synthesis of metallic isomer complexes containing ligands derivatives of pyridine and imines in trans position having high antitumoral activities, ii) the development of cationic complexes with biological activity, iii) the discovery of preferential nucleotides for the intercalation of metallic complexes in the double helix of DNA of cancerous cells, configuring irreparable lesions in the macromolecule and iv) the interaction of metallic complexes with other biological molecules, like proteins and peptides, through terminal amine groups, carboxylate groups, imidazolic group of histidine and mostly with the thiol group of methionine. Some of these interactions are related to drug nefrotoxicity effect, which understanding is of fundamental importance. v) Novel ortho-cyclopalladated compounds synthesized from p-isopropylbenzaldehyde thiosemicarbazone have been described with specific cytotoxic properties in tumor cells sensitive to cis-diamminedichloroplatinum(II). The lysosomal cysteine proteinases cathepsins B and L have been implicated in a variety of pathological conditions, especially in diseases involving tissue-remodeling states, such as tumor metastasis. Our research group is studying inhibition of Cathepsin B by new palladacycle compounds derived from N, Ndimethyl- 1-phenethylamine and having biphosphine ligands. New palladacycle compounds derived from N,N-dimethyl-1- phenethylamine and the ligand bis(diphenylphosphine)ferrocene were presented as effective antitumoral agents.

Keywords: Palladium complexes, palladacycle complexes, anticancer agents, biphosphine complexes, lysosomal drugs, antitumoral compounds, enzyme inhibition, drug design