Palladium(II) complexes: Structure, development and cytotoxicity from cisplatin analogues to chelating ligands with N stereocenters

Abstract

Even though platinum(II/IV) complexes are found to be very active as anticancer agents, they have many well-known limitations. These drawbacks reflect through severe side-effects due to damaging healthy tissue and resistance. Exploring non-platinum metal complexes emerged as essential since they might exhibit different mechanism of action as well as reduced side effects, than platinum(II)-based ones. In this review, the progress in the field of anticancer chemistry of palladium(II)-based complexes will be given highlighting the close relationship between their structural preferences and cytotoxic ability. Activity and structure of a significant number of palladium complexes described in literature will be conjoint, and probable in vivo mechanism of palladium(II) species discussed. It is shown that bidentate chelating amines (e.g. (S,S)-R2edda-type ligands; R2edda = O,O’-dialkyl-ethylenediamine-N,N’-diacete esters) as ligands could play a crucial role in the stability of complexes and their ability to express biological activity. Complexes with general formulae [PdCl2{(S,S)-R2edda-type}], demonstrate good to moderate antiproliferative activity versus various cancer cell lines with emphasizing of O,O’-dipropyl-(S,S)-ethylenediamine-N,N’-di-2-(4-methyl)pentanoate, [PdCl2(S,S)-(n-Pr)2eddl] (most powerful against chronic lymphocytic leukemia cells, CLL). Structural features and diastereoisomers arising from nitrogen coordination in square-planar palladium(II) complexes with bidentate κ2N,N’ or tridentate κ2N,N’κO, ligands will be summarized and discussed. In vitro cytotoxicity of these complexes on a number of tumor cell lines will give an insight in structure–activity relationships which may lead to the divergence from platinum based drugs. Additionally, an overview of antimicrobial activity is presented.