Cisplatin and zoledronic acid: two drugs combined in a Pt(II) complex with potential antitumor activity towards bone tumors and metastases

Treatment of primary bone malignancies comprises surgery, radiotherapy, chemotherapy, and analgesics. Platinum-based chemotherapeutics, such as cisplatin, are commonly used for the treatment of bone cancer but, despite their success, outcomes are limited by toxicity and resistance. Recently, dinuclear Pt complexes with a bridging geminal bisphosphonate ligand proved to be endowed with selective accumulation in bone tumors or metastases leading to improved efficacy and reduced systemic toxicity. Further improvement could be expected by the use of a bisphosphonate ligand with intrinsic pharmacological activity such as zoledronic acid (ZL). In the present work is reported the synthesis and full characterization of the dinuclear Pt(ii) complex [{cis-Pt(NH3)(2)}(2)(ZL)]HSO4 which combines two drugs with antitumor activity, cisplatin and zoledronic acid. Both drugs, individually, are already approved by the U.S. Food and Drug Administration and the European Medicinal Agency for clinical use. The in vitro cytotoxicity of the new Pt(ii)-ZL complex has been tested against a panel of human tumor cell lines.