A5000911713- Metal complexes synthesis and properties
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Lanthanide and Transition Metal Complexes
- Drug Transport and Resistance Mechanisms
- Nanoparticle-Based Drug Delivery
- Magnetism in coordination complexes
- Lung Cancer Research Studies
- Cancer therapeutics and mechanisms
- Lung Cancer Treatments and Mutations
- DNA and Nucleic Acid Chemistry
- Ferrocene Chemistry and Applications
- Trace Elements in Health
- Click Chemistry and Applications
- Protein Interaction Studies and Fluorescence Analysis
- Peptidase Inhibition and Analysis
- Free Radicals and Antioxidants
- Cell death mechanisms and regulation
- Histone Deacetylase Inhibitors Research
- Synthesis and Characterization of Heterocyclic Compounds
- Fibroblast Growth Factor Research
- Metal-Catalyzed Oxygenation Mechanisms
- Cell Adhesion Molecules Research
- Calpain Protease Function and Regulation
- Radiopharmaceutical Chemistry and Applications
University of Vienna
2016-2025
Medical University of Vienna
2013-2025
Comprehensive Cancer Center Vienna
2011-2023
Translational Research in Oncology
2016-2023
Czech Academy of Sciences, Institute of Inorganic Chemistry
2023
Institute of Inorganic Chemistry of the Slovak Academy of Sciences
2018-2021
Faculty (United Kingdom)
2017-2021
Austrian Economics Center
2016
University of Szeged
2013
University of Veterinary Medicine Vienna
2013
NKP-1339 is the first-in-class ruthenium-based anticancer drug in clinical development against solid cancer and has recently been studied successfully a phase I trial. Ruthenium compounds such as KP1019 (indazolium trans-[tetrachloridobis(1H-indazole)ruthenate(III)]) (the sodium salt analogue of KP1019, have high tumour targeting potential based (1) on their strong binding to serum proteins albumin transferrin well (2) activation reductive milieu. The redox activity ruthenium believed...
The first metal complexes of 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (Triapine) were synthesized. Triapine was prepared by a novel three-step procedure in 64% overall yield. In addition, series related ligands, namely, 2-formylpyridine thiosemicarbazone, 2-acetylpyridine 2-pyridineformamide and their N4-dimethylated derivatives (including the analogue Triapine) prepared, along with corresponding gallium(III) iron(III) general formula [M(L)2]+, where HL is respective...
A series of gallium(III) and iron(III) complexes with five different 4N-substituted α-N-heterocyclic thiosemicarbazones, viz., 2-acetylpyridine N,N-dimethylthiosemicarbazone (1), N-pyrrolidinylthiosemicarbazone (2), acetylpyrazine (3), (4), N-piperidinylthiosemicarbazone (5), the general formula [GaLCl2] (HL = 1 2) [ML2][Y] (M Ga, HL 1−5, Y PF6; M Fe, FeCl4 PF6) were synthesized characterized by elemental analysis, a number spectroscopic methods (NMR, IR, UV−vis), mass spectrometry, X-ray...
An oxaliplatin-based platinum(<sc>iv</sc>) drug which specifically binds to albumin after i.v. application led several complete responses in tumor-bearing mice.
Glutathione (GSH) is the most abundant thiol in mammalian cells and plays a crucial role maintaining redox cellular homeostasis. The thiols of two GSH molecules can be oxidized to disulfide GSSG. cytosolic GSH/GSSG ratio very high (>100), its reduction lead apoptosis or necrosis, which are interest cancer research. CuII ions efficient oxidants thiols, but with an excess GSH, CuIn(GS)m clusters formed, CuI slowly reoxidized by O2 at pH 7.4 even more lower pH. Here, aerobic oxidation was...
Abstract Clinical efficacy of oxaliplatin is frequently limited by severe adverse effects and therapy resistance. Acquired insensitivity to is, at least in part, associated with elevated levels glutathione (GSH). In this study we report on an oxaliplatin-based platinum(IV) prodrug, which releases L -buthionine- S , R -sulfoximine (BSO), inhibitor glutamate-cysteine ligase, the rate-limiting enzyme GSH biosynthesis. Two complexes bearing either acetate ( BSO-OxOAc ) or albumin-binding...
Maleimides remain very popular conjugation moieties in the fields of bio(in)organic chemistry and biotechnology. They are particularly interesting for endogenous albumin binding bloodstream to exploit enhanced permeability retention (EPR) effect increase tumor accumulation anticancer drugs. However, during drug development, insufficient aqueous solubility is frequently a limiting factor. In present study, four new maleimide linkers were synthesized containing water-soluble piperazine...
Maleimide-functionalised Pt(IV) complexes with highly selective binding properties to thiol groups were synthesised as precursors for of thiol-containing tumour-targeting molecules like human serum albumin.
The lipophilic character of novel carboplatin prodrugs was controlled by the choice axial ligand also influencing their cytotoxicity.
The development of receptor tyrosine-kinase inhibitors (TKIs) was a major step forward in cancer treatment. However, the therapy with TKIs is limited by strong side effects and drug resistance. aim this study design novel epidermal growth factor (EGFR) that are specifically activated malignant tissue. Thus, Co(III) -based prodrug strategy for targeted release an EGFR inhibitor triggered hypoxia solid tumor used. New chelating moieties were prepared tested their EGFR-inhibitory potential....
Abstract Maleimides are essential compounds for drug conjugation reactions via thiols to antibodies, peptides and other targeting units. However, one main drawback is the occurrence of thiol exchange with, example, glutathione resulting in loss ability. A new strategy overcome such retro‐Michael processes maleimide–thiol conjugates by stabilization thiosuccinimide a transcyclization reaction presented. This enables straightforward synthesis stable adducts drug‐conjugation applications.
Due to their high kinetic inertness and consequently reduced side reactions with biomolecules, Pt
Chemotherapy with platinum complexes is essential for clinical anticancer therapy. However, due to side effects and drug resistance, further improvement urgently needed. Herein, we report on triple-action platinum(IV) prodrugs, which, in addition tumor targeting via maleimide-mediated albumin binding, release the immunomodulatory ligand 1-methyl-d-tryptophan (1-MDT). Unexpectedly, structure–activity relationship analysis showed that mode of 1-MDT conjugation distinctly impacts reducibility...
We investigated the first oxaliplatin( iv ) complexes releasing acetylsalicylic acid (aspirin) upon reduction. The albumin-targeted derivative showed distinctly improved antitumor activity compared to asplatin, a recently reported cisplatin( analog.
Triapine (3-aminopyridine-2-carboxaldehyde thiosemicarbazone), which entered several phase I and II clinical trials as an antitumor chemotherapeutic agent, was found to possess intrinsic fluorescence properties (lambda(ex) = 360 nm), enabled us monitor the uptake intracellular distribution in living human cancer cells by microscopy.
Abstract The interactions of Cu II , Zn and Fe with Triapine (3‐aminopyridine‐2‐carbaldehyde thiosemicarbazone), which is currently undergoing phase clinical trials as a chemotherapeutic antitumour agent, were investigated in water/DMSO mixture. proton‐dissociation constants the ligands, stability coordination modes metal complexes formed determined by pH‐potentiometric, UV/Vis spectrophotometric, EPR, 1 H NMR spectroscopic ESI‐MS methods. Two N‐terminally dimethylated derivatives also...