Novel Ruthenium and Osmium Nitrosyl and Nitroxide Complexes: Synthesis, Structure, Reactivity and Antiproliferative Activity in Vitro – VILYGRu

Metal coordination compounds have had a great impact in cancer chemotherapy especially since the discovery in the 60?s of the Cisplatin, a platinum complex which is still in wide clinical use for the treatment of different type of cancer despite a high toxicity with undesirable side effects. Although this field has witnessed major advances over the last few decades, clinicians still face the problem of the lack of specific chemotherapeutic agents able to yield the desired clinical therapeutic effect for a particular tumor and patient, with diminished side effects. It is an acute question considering the continuous increase in cancer incidence on the overall population and the role of chemotherapy and metal drug will further increase over the next decades. The challenge for a conventional coordination chemist is thus to discover novel and specific metal based chemotherapeutic agents. In this context ruthenium(II) and ruthenium(III) complexes are the subject of current investigation as promising anticancer drug candidates and one ruthenium complex developed by the Austrian team has finished phase I clinical trials as an anticancer agent against primary tumors and metastases. The goal of the present proposal is the synthesis of new ruthenium complexes able of releasing nitric oxide (NO) in tumour cells in a controlled manner upon reduction by biological reductants or by photoactivation. Studies of their redox activity of the complexes will be carried out by electrochemistry and EPR spectroscopy. The anticancer activity of the best compounds will be tested in vitro. Analogous osmium and nitroxide complexes will be also investigated. This proposal brings together chemists and spectroscopists that have complementary expertise in the area of coordination chemistry, spectroscopy and medicinal chemistry.