title: CZE-ICP-MS as a tool for studying the hydrolysis of ruthenium anticancer drug candidates and their reactivity towards the DNA model compound dGMP.
abstract: Elucidating the mode of action and thereby opening the way to the design of chemotherapeutic agents is one of the major goals of metal-based anticancer research. Hydrolysis and DNA binding play an important role for pharmaceutical formulation and for exerting anticancer activity. Herein, for the first time the application of capillary zone electrophoresis-inductively-coupled plasma mass spectrometry (CZE-ICP-MS) for studying the hydrolytic stability and the binding of the ruthenium anticancer drug candidates KP418, KP1019, and RAPTA-C to dGMP is described. RAPTA-C was found to hydrolyze fastest and showed the highest reactivity toward the DNA model compound, whereas KP418 was the most stable compound in both these respects.
authors.affiliation: Institute of Inorganic Chemistry, University of Vienna, Waehringer Street 42, A-1090 Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Groessl
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
authors.forename: Bernhard K
authors.initials: BK
authors.lastname: Keppler
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry*; D000081007:Cymenes; D003848:Deoxyguanine Nucleotides / Q000737:chemistry*; D004355:Drug Stability; D019075:Electrophoresis, Capillary / Q000379:methods*; D006868:Hydrolysis; D007191:Indazoles / Q000737:chemistry*; D013058:Mass Spectrometry / Q000379:methods*; D009942:Organometallic Compounds / Q000737:chemistry*; D017975:Ruthenium Compounds / Q000737:chemistry*
chemical_list: D000970:Antineoplastic Agents; D000081007:Cymenes; D003848:Deoxyguanine Nucleotides; D007191:Indazoles; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C530402:dichloro(4-cymene)(1,3,5-triaza-7-phosphatricyclo(3.3.1.1)decane)ruthenium(II); C521720:imidazolium tetrachlorobis(1H-imidazole)ruthenate(III); C499292:indazolium trans-(tetrachlorobis(1H-indazole)ruthenate (III)); C007257:2'-deoxyguanosine 5'-phosphate