Organometallic and coordination rhenium compounds and their potential in cancer therapy

• Coordination compounds of rhenium and their evaluation in biological assays. • Most cytotoxic rhenium coordination compounds according to their IC 50 values. • Basic concepts and structural similarities for cytotoxicity of rhenium compounds. • List of coordination compounds of rhenium currently evaluated in clinical trials. • Comparison of cytotoxic Re compounds and the compounds included in clinical trials. This review focuses on cytotoxic rhenium compounds in terms of IC 50 values, their mode of action in biological systems and their status in clinical trials. Biological studies of different rhenium compounds ordered by the oxidation state of rhenium are presented. Numerous rhenium complexes are reported, with the greatest number of compounds containing a Re(I)(CO) 3 + core. A wide range of complexes has been designed using a combination of organometallic ligands, N- or S-based ligands, peptides, multidentate ligands and oxo groups. Design concepts based on membrane permeability and lipophilicity, membrane receptor targets and specific enzyme targets are presented. The cytotoxicity parameter IC 50 is shown for organometallic compounds, coordination complexes, clusters and Re(oxo) complexes. In addition, a brief summary of in vivo studies is given. A further summary of rhenium compounds subjected to clinical trials is presented to provide information about the classes of rhenium compounds that have been tested in human beings and the approaches used in these studies. Moreover, the comparability of the IC 50 values among the cytotoxicity studies is critically assessed to provide the basis for a summary of the most potent rhenium compounds according to their reported IC 50 values for each type of cancer. The summary of the structures for the most cytotoxic complexes allows the identification of structural similarities and basic features that could lead to their cytotoxicity and might be useful for future investigations. Finally, the information from the analysis of the rhenium compounds subjected to cellular studies is compared to data on the rhenium compounds that have been involved in in vivo evaluation and clinical trials.