title: Synthesis, characterization, and cytotoxicity of dinuclear platinum-bisphosphonate complexes to be used as prodrugs in the local treatment of bone tumours.
abstract: For over 30 years cisplatin has been one of the most active antitumour agents in clinical use, nevertheless research for overcoming cisplatin toxicity and resistance or for improving its efficacy has never ceased. In this context we have recently proposed dinuclear Pt complexes with bridging geminal bisphosphonates as novel Pt-prodrugs with potential activity at the bone surface after embedment in inorganic matrices and implantation at the tumour site. In the present paper we report the synthesis and full characterization of four new platinum complexes having a dinuclear structure with a bisphosphonate (2-ammonium-1-hydroxyethane-1,1-diyl-bisphosphonate or 3-ammonium-1-hydroxypropane-1,1-diyl-bisphosphonate, AHBP-H and PAM-H, respectively) acting as a bridging ligand between two platinum moieties (cis-[Pt(NH(3))(2)](2+), directly related to cisplatin, and [Pt(cis-1,4-DACH)](2+), known to be able to overcome the cisplatin resistance). Moreover, as a preliminary investigation, the in vitro cytotoxicity of the new complexes has been evaluated on a panel of 13 human tumour cell lines including cisplatin- and multidrug-resistant sublines.
authors.affiliation: Dipartimento Farmaco-Chimico, Università degli Studi di Bari A. Moro, Via E. Orabona 4, 70125, Bari, Italy.
authors.forename: Nicola
authors.initials: N
authors.lastname: Margiotta
authors.forename: Rosa
authors.initials: R
authors.lastname: Ostuni
authors.forename: Valentina
authors.initials: V
authors.lastname: Gandin
authors.forename: Cristina
authors.initials: C
authors.lastname: Marzano
authors.forename: Sara
authors.initials: S
authors.lastname: Piccinonna
authors.forename: Giovanni
authors.initials: G
authors.lastname: Natile
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001859:Bone Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D004164:Diphosphonates / Q000737:chemistry*; D019008:Drug Resistance, Neoplasm; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010984:Platinum / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D004164:Diphosphonates; D011355:Prodrugs; D010984:Platinum