Synthesis and Cytotoxic Activity of Ruthenium Complexes with Ethacrynic Acid Derived Ligands

There is currently high interest in the design of organic motifs containing biologically-active fragments to be incorporated within suitable metal complexes, in order to confer them enhanced anticancer activity. One of the possible approaches regards the inclusion of the skeleton of ethacrynic acid, which is an effective inhibitor of glutathione transferases (GST), i.e. a family of cytosolic detoxification enzymes associated with drug resistance in primary and metastatic tumours [1]. Triphenylphosphine and pyridine-based molecules functionalized with the ethacrynic acid skeleton were synthesized and incorporated as ligands within Ru(II) arene and Ru(III) NAMI-A type complexes, respectively (see Scheme) [2]. All of the new compounds were characterized by analytical and spectroscopic methods, and by single-crystal X-ray diffractometry in one case. Preliminary cytotoxic studies will be presented.