1. From hydrolytically labile to hydrolytically stable Ru(II)-arene anticancer complexes with carbohydrate-derived co-ligands
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Hanif, M., Meier, S. M., Kandioller, W., Bytzek, A., Hejl, M., Hartinger, C. G., Nazarov, A. A., Arion, V. B., Jakupec, M. A., Dyson, P. J., and Keppler, B. K.
- Subjects
Carbohydrate ligands ,Bioorganometallic chemistry ,Microemulsion Electrokinetic Chromatography ,Aquation ,Drugs ,Icp-Ms ,Pta Complexes ,Anticancer activity ,Ruthenium ,Titanocene Dichloride ,Platinum Complexes ,Organometallic Ruthenium Compound ,In-Vitro ,Medicinal Applications ,Mass-Spectrometry - 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(eta(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)ruthenium(II) and oxalato(eta(6)-p-cymene)(3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-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 H-1 and P-31(H-1) 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. (C) 2010 Elsevier Inc. All rights reserved.