TRANSITION METAL ION COMPLEXES AS POTENTIAL ANTITUMOR AGENTS

Abstract

Discovery of the antitumor activity of platinum complex, cisplatin, cis-Pt(NH3)2Cl2, and later carboplatin and oxaliplatin, led to the intensive investigation of the potential antitumor activity of the huge number of platinum complexes. Furthermore, it is well-known that platinum complexes express toxicity, numerous side effects and resistance, so the scientists make a lot of efforts to synthetize, beside Pt(II) and Pt(IV), other non-platinum compounds with potential antitumor activity, such as Pd(II), Ru(II/III) and Au(III) complexes. The goal of this study is to summarize the results of the investigation of the interactions between some mononuclear, homo- and hetero-polynuclear Pt(II), Pd(II), Ru(II/III) and Au(III) complexes with different sulfur- and nitrogen-donor biologically relevant nucleophiles. Among mononuclear complexes, the compounds with aromatic terpy (tepyridine) or bpma (bis-(2- pyridylmethyl)amine) and aliphatic dien (diethylentriamine) nitrogen-containing inert ligands were studied. Different homo- and hetero-polynuclear complexes with pz (pyrazine) or 4,4’-bipy (4,4’- bipyridine) as bridging and mostly en (ethylenediamine), bipy (2,2’-bipyridine) and dach (trans-1,2- diaminocyclohexane) as inert ligands were studied as well. The research was focused on the connection between the structure and the mechanisms of interactions with different biomolecules, such as L- cysteine (L-Cys), L-methionine (L-Met), tripeptide glutathione (GSH), guanosine-5’-monophosphate (5’-GMP), DNA and bovine serum albumin (BSA). Some of these complexes were selected for in vitro studies of the cytotoxicity on different tumor cell lines. Observed results contribute a lot as a guidance for the future design and determination of the structure-activity relationship (SAR) of different transition metal ion complexes.