A5058477570- X-ray Diffraction in Crystallography
- Crystallization and Solubility Studies
- Metal complexes synthesis and properties
- Ferrocene Chemistry and Applications
- Click Chemistry and Applications
- Analytical chemistry methods development
- Crystallography and molecular interactions
- Trace Elements in Health
- RNA Interference and Gene Delivery
- Cell Adhesion Molecules Research
- Chemical Synthesis and Analysis
- Skin and Cellular Biology Research
- Synthesis and Characterization of Heterocyclic Compounds
- Chromium effects and bioremediation
- Advanced biosensing and bioanalysis techniques
- Liver Disease Diagnosis and Treatment
- Spine and Intervertebral Disc Pathology
- Analytical Chemistry and Chromatography
- Polysaccharides and Plant Cell Walls
- Lanthanide and Transition Metal Complexes
- Nerve injury and regeneration
- Peripheral Nerve Disorders
- Dendrimers and Hyperbranched Polymers
- Fungal and yeast genetics research
- Signaling Pathways in Disease
University of Vienna
2016-2021
Medical University of Vienna
2017-2018
Faculty (United Kingdom)
2018
FH Campus Wien
2017
Abstract Organometallic metal(arene) anticancer agents require ligand exchange for their activity and this is generally believed to confer low selectivity potential cellular targets. However, using an integrated proteomics‐based target‐response profiling approach as a potent hypothesis‐generating procedure, we found unexpected target of ruthenium(arene) pyridinecarbothioamide (plecstatin) plectin, scaffold protein cytolinker, which was validated in plectin knock‐out model vitro. Plectin...
Herein we report the synthesis, anticancer potency in vitro, biomolecule interaction, and preliminary mode of action studies a series cyclometalated 1,2,3-triazole-derived ruthenium(II) (2a-e) osmium(II) (3a-e) organometallics general form [(η6-p-cym)RuCl(κ2-C^N-L)] with varying substituents postion 1 1,2,3-triazole moiety. These cyclometalates were characterized by standard analytical methods their structures unambiguously assigned single crystal X-ray crystallography. The activity these...
Lipophilicity is a crucial parameter for drug discovery, usually determined by the logarithmic partition coefficient (Log P) between octanol and water. However, available detection methods have restricted widespread use of in inorganic medicinal chemistry, recent investigations shifted towards chromatographic lipophilicity parameters, frequently without conversion to derive Log P. As high-performance liquid chromatography (HPLC) instruments are readily research groups, HPLC-based method...
<bold>Macromolecular drug conjugates</bold>: Polymer conjugation reduces local side effects and tumor growth <italic>in vivo</italic>.
Two isosteric organometallic drug candidates revealed distinct <italic>in vivo</italic> antitumour activities and spatial distributions in mouse tissues.
Size-exclusion chromatography-inductively coupled plasma-mass spectrometry (SEC-ICP-MS) was used to study the serum-binding preferences of two metallodrugs with anticancer activities in vivo, namely organoruthenium compound plecstatin-1 and its isosteric osmium analog. The complexes were administered intraperitoneally into mice bearing a CT-26 tumor. Comparing total metal content mouse whole blood serum underlined that are mainly located not cellular fraction samples. In serum, both...
The high mortality rate of lung cancer patients and the frequent occurrence side effects during therapy demonstrate need for more selective targeted drugs. An important well-established target treatment is occasionally mutated epidermal growth factor receptor (EGFR). As platinum(II) drugs are still most therapeutics against cancer, we synthesized in this study first platinum(IV) complexes coupled to EGFR-targeting peptide LARLLT (and shuffled RTALLL as reference). Notably, HPLC–MS...
An unsymmetrically carboxylated platinum(IV) analogue of oxaliplatin was coupled to low‐generation polyamidoamine dendrimers (PAMAM) with amino‐terminated surfaces [generations two (G‐2) and four (G‐4)]. 1D 2D diffusion NMR spectroscopy high‐resolution HPLC–MS/MS were used characterise the platinum complexes drug–dendrimer conjugates. The average loads complex per dendrimer determined by inductively plasma MS (ICP‐MS), maximum 38 % (six units molecule) for smaller G‐2 34 (22 G‐4 obtained. As...
Increasing the specificity of cancer therapy, and thereby decreasing damage to normal cells, requires targeting cancer-cell specific features. The αvβ6 integrin is a receptor involved in cell adhesion frequently up-regulated cells compared cells. We have selected peptide ligand reported bind specifically β6 synthesized suite multispecific molecules explore potential for A combination solid-phase synthesis chemoselective ligations was used synthesize multifunctional composed...
Rho kinase activity in hepatic stellate cells (HSCs) is associated with activation, transformation and contraction of these cells, leading to extracellular matrix production portal hypertension liver cirrhosis. Inhibition rho can reduce activities, but may also lead side effects, for instance systemic hypotension. This be circumvented by liver-specific delivery a inhibitor effector cells. Therefore, we targeted the Y27632 key pathogenic fibrosis, i.e. myofibroblasts including activated HSCs...
A series of 11 novel ruthenium(ii) arene complexes [Ru(p-cym)(trzC^N)L]NO3 based on the cycloruthenated 1,2,3-triazole scaffold (trzC^N) bearing different N- or S-donor leaving groups (L) were prepared. These exhibited strongly diverging pH-dependent stability profiles, but consistently exerted antiproliferative effects in low micromolar range three cancer cell lines (A549, SW480, CH1/PA-1). The interaction with biomolecules was correlated to dissociation monodentate group. Under oxidative...
An orally active osmium anticancer compound was reliably quantified in the organs of treated mice by inductively coupled plasma-mass spectrometry (ICP-MS) adding a stabilizing solution consisting ascorbic acid, thiourea and EDTA during sample preparation avoiding oxidizing conditions. The limits detection (LOD) quantification (LOQ) 189Os were determined liver tissue to be 0.02 0.075 μg kg-1, respectively. In spiked tissue, internal precision showed relative standard deviation (RSD) 4%,...
Abstract Metallorganische Tumortherapeutika werden durch Ligandenaustausch aktiviert, und es wird gemeinhin angenommen, dass die resultierenden aktivierten Spezies geringe Selektivität für potenzielle zelluläre Ziele zeigen. Durch ein Proteomik‐basiertes Ziel‐Antwort‐Profiling konnte jedoch nachgewiesen werden, Ruthenium‐Aren‐Pyridincarbothioamid (Plecstatin) eine unerwartet hohe Plectin, Strukturprotein Vernetzer des Zytoskeletts, zeigt, was in einem Plectin‐Knock‐out‐Modell vitro validiert...
A series of 2-phenylbenzothiazole derivatives and their corresponding organometallic ruthenium(II) osmium(II) complexes were synthesized, designed to exploit both, the attributes half-sandwich transition metal scaffold bioactivity spectrum applied 2-phenylbenzothiazoles. All synthesized compounds characterized via standard analytical methods. The obtained organometallics showed antiproliferative activity in low µM range are thus at least an order magnitude more potent than free ligands....
Fine-tuning of the properties a recently reported 1,3-indandione-based organoruthenium complex is attempted to optimize stability under physiological conditions. Previous work has shown its capacity inhibiting topoisomerase IIα; however, fast aquation leads undesired reactions and ligand cleavage in blood stream before tumor tissue reached. Exchange chlorido for six different N-donor ligands resulted new analogs that were stable at pH 7.4 8.5. Only lowered level, as encountered extracellular...
Introduction: Current imaging modalities for peripheral nerves display the nerve's structure but not its function. Based on a capacity axonal transport, it may be visualized by targeted application of contrast agent and assessing distribution through radiological imaging, thus revealing continuity. This concept has been explored, however, potentially guide treatment nerve injuries. In this experimental proof-of-concept study, we tested MRI after administering gadolinium-based agents which...
Metallhaltige Tumortherapeutika werden oft als Prodrugs mit absichtlich geringer Selektivität konzipiert. Dagegen beschreiben S. M. Meier, C. Gerner et al. in der Zuschrift auf 8379 die unerwartet große eines metallorganischen Ruthenium(II)-Komplexes, einer Kombination Proteomik-basierter Methoden, dem Ziel-Antwort-Profiling, erhalten wurde. Plectin wurde zentrale zelluläre Zielverbindung identifiziert. Das Plectin-Targeting wechselwirkt Mikrotubulinetzwerk und könnte daher zur...