title: Development of organometallic ruthenium-arene anticancer drugs that resist hydrolysis.
abstract: With a view to develop drugs that could resist hydrolysis in aqueous media, organometallic arene-capped ruthenium(II) 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (RAPTA) complexes bearing chelating carboxylate ligands have been prepared and studied. The new complexes, Ru(eta6-cymene)(PTA)(C2O4) (1) and Ru(eta6-cymene)(PTA)(C6H6O4) (2), were found to be highly soluble and kinetically more stable than their RAPTA precursor that contains two chloride ligands in place of the carboxylate ligands. They were also able to resist hydrolysis in water and exhibited significantly lower pKa values. Importantly, they showed a similar order of activity in inhibiting cancer cell-growth proliferation (as determined by in vitro assays) and exhibited oligonucleotide binding characteristics (as evidenced by matrix-assisted laser desorption ionization mass spectrometry) similar to those of the RAPTA precursor, hence realizing a strategy for developing a new generation of stable and highly water-soluble RAPTA adducts.
authors.affiliation: Institut des Sciences et Ingénierie Chimiques, Ecole Polytechnique Fédérale de Lausanne (EPFL), CH-1015 Lausanne, Switzerland.
authors.forename: Wee Han
authors.initials: WH
authors.lastname: Ang
authors.forename: Elisa
authors.initials: E
authors.lastname: Daldini
authors.forename: Claudine
authors.initials: C
authors.lastname: Scolaro
authors.forename: Rosario
authors.initials: R
authors.lastname: Scopelliti
authors.forename: Lucienne
authors.initials: L
authors.lastname: Juillerat-Jeannerat
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D001555:Benzene Derivatives / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D006801:Humans; D006868:Hydrolysis; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology; D012428:Ruthenium / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D001555:Benzene Derivatives; D009942:Organometallic Compounds; D012428:Ruthenium