Journal ArticleDOI
In vitro anticancer activity and biologically relevant metabolization of organometallic ruthenium complexes with carbohydrate-based ligands.
Isabella Berger,Muhammad Hanif,Alexey A. Nazarov,Alexey A. Nazarov,Christian G. Hartinger,Christian G. Hartinger,Roland O. John,Maxim L. Kuznetsov,Michael Groessl,Frédéric Schmitt,Olivier Zava,Florian Biba,Vladimir B. Arion,Markus Galanski,Michael A. Jakupec,Lucienne Juillerat-Jeanneret,Paul J. Dyson,Bernhard K. Keppler +17 more
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TLDR
In vitro studies revealed that the 3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside complex is the most cytotoxic compound in human cancer cell lines (IC50 values from 30 to 300 microM depending on the cell line).Abstract:
The synthesis and in vitro anticancer activity of dihalogenido(eta6-p-cymene)(3,5,6-bicyclophosphite-alpha-D-glucofuranoside)ruthenium(II) complexes are described. The compounds were characterized by NMR spectroscopy and ESI mass spectrometry, and the molecular structures of dichlorido-, dibromido- and diiodido(eta6-p-cymene)(3,5,6-bicyclophosphite-1,2-O-isopropylidene-alpha-D-glucofuranoside)ruthenium(II) were determined by X-ray diffraction analysis. The complexes were shown to undergo aquation of the first halido ligand in aqueous solution, followed by hydrolysis of a P--O bond of the phosphite ligand, and finally formation of dinuclear species. The hydrolysis mechanism was confirmed by DFT calculations. The aquation of the complexes was markedly suppressed in 100 mM NaCl solution, and notably only very slow hydrolysis of the P--O bond was observed. The complexes showed affinity towards albumin and transferrin and monoadduct formation with 9-ethylguanine. In vitro studies revealed that the 3,5,6-bicyclophosphite-1,2-O-cyclohexylidene-alpha-D-glucofuranoside complex is the most cytotoxic compound in human cancer cell lines (IC50 values from 30 to 300 microM depending on the cell line).read more
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Arene ruthenium complexes as anticancer agents
TL;DR: Neutral or cationic arene ruthenium complexes providing both hydrophilic as well as hydrophobic properties due to the robustness of the rUThenium-arene unit hold a high potential for the development of metal-based anticancer drugs.
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Challenges and Opportunities in the Development of Organometallic Anticancer Drugs
TL;DR: A brief overview of the subject together with recent pertinent examples can be found in this article, where the properties of organometallic compounds that lend themselves to medical applications, the main current approaches used, and possible avenues for future research are identified.
Journal ArticleDOI
Structure–activity relationships for ruthenium and osmium anticancer agents – towards clinical development
Samuel M. Meier-Menches,Samuel M. Meier-Menches,Christopher Gerner,Walter Berger,Walter Berger,Christian G. Hartinger,Bernhard K. Keppler +6 more
TL;DR: Global structure-activity relationships are discussed for ruthenium and osmium metallodrugs with respect to in vitro antiproliferative/cytotoxic activity and in vivo tumor-inhibiting properties, as well as pharmacokinetics.
Journal ArticleDOI
Targeted and multifunctional arene ruthenium chemotherapeutics
Gregory S. Smith,Bruno Therrien +1 more
TL;DR: An ever-increasing number of papers dealing with the integration of ruthenium complexes with biologically active molecules to derive bioorganometallic molecules of chemotherapeutic significance have been published in recent years, with the emphasis on the combination of photosensitizers with rutenium complexes for the preparation of novel multifunctional photodynamic therapy agents.
Journal ArticleDOI
Opening the lid on piano-stool complexes: An account of ruthenium(II)–arene complexes with medicinal applications
TL;DR: The origins of the field are described, the design of compounds that inhibit enzymes are designed, the application of multinuclear systems to act as drug delivery vehicles, and the development of bioanalytical and biophysical methods are highlighted to help elucidate the mechanisms by which these compounds function.
References
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Quantum Calculation of Molecular Energies and Energy Gradients in Solution by a Conductor Solvent Model
Vincenzo Barone,Maurizio Cossi +1 more
TL;DR: In this paper, a new implementation of the conductor-like screening solvation model (COSMO) in the GAUSSIAN94 package is presented, which allows Hartree−Fock (HF), density functional (DF) and post-HF energy, and HF and DF gradient calculations: the cavities are modeled on the molecular shape, using recently optimized parameters, and both electrostatic and nonelectrostatic contributions to energies and gradients are considered.
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Energy-adjustedab initio pseudopotentials for the second and third row transition elements
TL;DR: In this paper, nonrelativistic and quasirelativisticab initio pseudopotentials substituting the M(Z−28)+-core orbitals of the second row transition elements and the M (Z−60)+- core orbitals, respectively, and optimized (8s7p6d)/[6s5p3d]-GTO valence basis sets for use in molecular calculations were generated.