title: From hydrolytically labile to hydrolytically stable Ru(II)-arene anticancer complexes with carbohydrate-derived co-ligands.
abstract: The synthesis, characterization, reactivity and in vitro anticancer activity of a series of Ru(II)-arene complexes with carbohydrate-derived phosphite and biscarboxylato co-ligands are reported. The compounds were characterized by NMR spectroscopy and electrospray ionization (ESI) mass spectrometry, and the molecular structures of oxalato(η(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-α-D-glucofuranoside)ruthenium(II) and oxalato(η(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-α-D-glucofuranoside)ruthenium(II) were determined by X-ray diffraction analysis. In contrast to their dichlorido counterparts, the biscarboxylato complexes did not exhibit significant reactivity towards biomolecules, such as cysteine, methionine, ubiquitin or the DNA model 5'-GMP, and resist hydrolysis; no hydrolytic species were detected by (1)H and (31)P{(1)H} NMR spectroscopy over several days. These structural alterations led to a decrease in the tumor-inhibiting potency of the compounds in human cancer cell lines.
authors.affiliation: University of Vienna, Institute of Inorganic Chemistry, Waehringer Str. 42, A-1090 Vienna, Austria.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Hanif
authors.forename: Samuel M
authors.initials: SM
authors.lastname: Meier
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Kandioller
authors.forename: Anna
authors.initials: A
authors.lastname: Bytzek
authors.forename: Michaela
authors.initials: M
authors.lastname: Hejl
authors.forename: Christian G
authors.initials: CG
authors.lastname: Hartinger
authors.forename: Alexey A
authors.initials: AA
authors.lastname: Nazarov
authors.forename: Vladimir B
authors.initials: VB
authors.lastname: Arion
authors.forename: Michael A
authors.initials: MA
authors.lastname: Jakupec
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 / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D000081007:Cymenes; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D006868:Hydrolysis; D020128:Inhibitory Concentration 50; D008024:Ligands; D008314:Malonates / Q000737:chemistry; D008968:Molecular Conformation; D009942:Organometallic Compounds / Q000737:chemistry; D009992:Osmium; D010070:Oxalates / Q000737:chemistry; D012428:Ruthenium; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D000081007:Cymenes; D008024:Ligands; D008314:Malonates; D009942:Organometallic Compounds; D010070:Oxalates; C530402:dichloro(4-cymene)(1,3,5-triaza-7-phosphatricyclo(3.3.1.1)decane)ruthenium(II); D009992:Osmium; D012428:Ruthenium; C030290:malonic acid