From hydrolytically labile to hydrolytically stable Ru(II)-arene anticancer complexes with carbohydrate-derived co-ligands

• Published in: Journal of inorganic biochemistry 2011-02, Vol.105 (2), p.224-231
• Main Authors: Hanif, Muhammad, Meier, Samuel M, Kandioller, Wolfgang, Bytzek, Anna, Hejl, Michaela, Hartinger, Christian G, Nazarov, Alexey A, Arion, Vladimir B, Jakupec, Michael A, Dyson, Paul J, Keppler, Bernhard K
• Format: Article
• Language: English
• Subjects: Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Cell Survival - drug effects; Coordination Complexes - chemical synthesis; Coordination Complexes - chemistry; Coordination Complexes - pharmacology; Crystallography, X-Ray; Drug Screening Assays, Antitumor; Humans; Hydrolysis; Inhibitory Concentration 50; Ligands; Malonates - chemistry; Molecular Conformation; Organometallic Compounds - chemistry; Osmium; Oxalates - chemistry; Ruthenium; Structure-Activity Relationship
• ISSN: 1873-3344
• DOI: 10.1016/j.jinorgbio.2010.10.004

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.