A5091207563- Metal complexes synthesis and properties
- Crystallization and Solubility Studies
- X-ray Diffraction in Crystallography
- Mycotoxins in Agriculture and Food
- Sulfur Compounds in Biology
- Drug Transport and Resistance Mechanisms
- Receptor Mechanisms and Signaling
- Nanoparticle-Based Drug Delivery
- Trace Elements in Health
- Nanocluster Synthesis and Applications
- Free Radicals and Antioxidants
- Endoplasmic Reticulum Stress and Disease
- Pharmacological Receptor Mechanisms and Effects
- Ferrocene Chemistry and Applications
- Fungal Plant Pathogen Control
- Neuropeptides and Animal Physiology
- Effects of Radiation Exposure
- Transgenic Plants and Applications
- Phosphodiesterase function and regulation
- Autophagy in Disease and Therapy
- Mast cells and histamine
- Lanthanide and Transition Metal Complexes
- Photodynamic Therapy Research Studies
- Graphene and Nanomaterials Applications
- Nanoplatforms for cancer theranostics
University of Vienna
2023-2025
Comprehensive Cancer Center Vienna
2016-2024
Medical University of Vienna
2016-2024
Phosphoglycerate dehydrogenase (PHGDH) has emerged as a crucial factor in macromolecule synthesis, neutralizing oxidative stress, and regulating methylation reactions cancer cells, lymphocytes, endothelial cells. However, the role of PHGDH tumor-associated macrophages (TAMs) is poorly understood. Here, we found that T helper 2 (Th2) cytokine interleukin-4 tumor-conditioned media upregulate expression promote immunosuppressive M2 macrophage activation proliferation. Loss disrupts cellular...
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...
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...
Abstract Due to their high biological activity, thiosemicarbazones have been developed for treatment of diverse diseases, including cancer, resulting in multiple clinical trials especially the lead compound Triapine. During last years, a novel subclass anticancer has attracted substantial interest based on enhanced cytotoxic activity. Increasing evidence suggests that double-dimethylated Triapine derivative Me 2 NNMe differs from not only its efficacy but also mode action. Here we show -...
One of the most promising classes iron chelators are α-N-heterocyclic thiosemicarbazones with Triapine as prominent representative. In several clinical trials showed anticancer activity against hematological diseases, however, studies on solid tumors failed due to widely unknown reasons. Some years ago, it was recognized that "terminal dimethylation" can lead a more than 100-fold increased activity, probably interactions cellular copper depots. To better understand structural requirements...
COTI-2 is a novel anticancer thiosemicarbazone in phase I clinical trial. However, the effects of metal complexation (a main characteristic thiosemicarbazones) and acquired resistance mechanisms are widely unknown. Therefore, this study, copper iron complexes were synthesized evaluated for their activity impact on drug comparison to metal-free thiosemicarbazones. Investigations using Triapine-resistant SW480/Tria newly established COTI-2-resistant SW480/Coti cells revealed distinct...
Due to their significant biological activity, thiosemicarbazones (TSCs) are promising candidates for anticancer therapy. In part, the efficacy of TSCs is linked ability chelate essential metal ions such as copper and iron. Triapine, best-studied TSC, has been tested clinically with results in hematological diseases. During past few years, a novel subclass improved activity was found induce paraptosis, recently characterized form cell death. The aim this study identify structural chemical...
Malignant pleural mesothelioma (MPM), an aggressive malignancy affecting surfaces, occurs in three main histological subtypes. The epithelioid and sarcomatoid subtypes are characterized by cuboid fibroblastoid cells, respectively. biphasic subtype contains a mixture of both. expresses markers epithelial-mesenchymal transition (EMT) confers the worst prognosis, but signals pathways controlling EMT MPM not well understood. We demonstrate that treatment with FGF2 or EGF induced morphology...
Abstract We have recently demonstrated that riboflavin ( Rf ) functions as unconventional bioorthogonal photocatalyst for the activation of Pt IV prodrugs. In this study, we show how combination light and with two prodrugs is a feasible strategy light-mediated pancreatic cancer cell death induction. Capan-1 cells, which high tolerance against photodynamic therapy, -mediated cisplatin carboplatin cis , trans -[Pt(NH 3 2 (Cl) (O CCH CH CO H) ] 1 (CBDCA)(O where CBDCA = cyclobutane...
COTI-2 is currently being evaluated in a phase I clinical trial for the treatment of gynecological and other solid cancers. As thiosemicarbazone, this compound contains an N,N,S-chelating moiety is, therefore, expected to bind endogenous metal ions. However, besides zinc, interaction properties have not been investigated detail so far. This unexpected, as we recently shown that forms stable ternary complexes with copper glutathione, which renders drug substrate resistance efflux transporter...
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...
Bottlebrush polymers are highly promising as unimolecular nanomedicines due to their unique control over the critical parameters of size, shape and chemical function. However, since they prepared from biopersistent carbon backbones, most known bottlebrush non-degradable thus unsuitable for systemic therapeutic administration. Herein, we report design synthesis novel poly(organo)phosphazene-g-poly(α-glutamate) (PPz-g-PGA) with exceptional structure molecular dimensions (Dh ≈ 15-50 nm). These...
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...
α-N-Heterocyclic thiosemicarbazones are among the most promising ribonucleotide reductase inhibitors identified so far. Triapine, prominent representative of this class substances, has been investigated in multiple phase I and II clinical trials. With regard to practice, Triapine showed activity against hematological diseases, but ineffectiveness a variety solid tumors. However, reasons still vague amount ADME (absorption, distribution, metabolism excretion) data for available literature is...
The increasing importance of sigma-2 receptor as target for the diagnosis and therapy tumors paves way development innovative optically traceable fluorescent probes tumor cell contrast therapeutic agents. Here, a novel hybrid organic-inorganic nanostructure is developed by combining superior properties inorganic quantum dots (QDs), coated with hydrophilic silica shell (QD@SiO2 NPs), versatility shell, high selectivity two synthetic ligands, namely,...
// Walter Miklos 1 , Petra Heffeter 1, 3 Christine Pirker Sonja Hager Christian R. Kowol 2, Sushilla van Schoonhoven Mirjana Stojanovic Bernhard K. Keppler Berger Department of Medicine I, Institute Cancer Research and Comprehensive Center, Medical University Vienna, A-1090 Austria 2 Inorganic Chemistry, Platform "Translational Therapy Research", Vienna Correspondence to: Berger, email: walter.berger@meduniwien.ac.at Keywords: triapine-resistance, phosphodiesterase, Epac, Rap1, integrin...
α-N-Heterocyclic thiosemicarbazones such as triapine and COTI-2 are currently investigated anticancer therapeutics in clinical trials. However, was widely inactive against solid tumor types. A likely explanation is the short plasma half-life time fast metabolism. One promising approach to overcome these drawbacks encapsulation of drug into nanoparticles (passive drug-targeting). In a previous work we showed that it not possible stably encapsulate free liposomes. Hence, this manuscript...
Thiosemicarbazones (TSCs) are a class of biologically active compounds with promising anticancer activity. Their typical mechanism, especially the clinically far developed representative Triapine, is chelation iron (Fe), Fe-containing enzyme ribonucleotide reductase as primary intracellular target. However, for subclass terminally disubstituted, nanomolar-active derivatives like Dp44mT and Me2NNMe2, recent findings suggest that chelation, stability, reduction properties copper(II) (Cu)...
Screening for new bioactive microbial metabolites, we found a novel okaramine derivative, which propose the trivial name lemmokaramine, as well two already known congeners - H and J responsible antimicrobial activity of recently described microscopic filamentous fungus, Keratinophyton lemmensii BiMM-F76 (= CCF 6359). In addition, substances, cyclohexyl denominated lemmensihexol tetrahydroxypyrane lemmensipyrane, were purified characterized. The compounds isolated from culture extract fungus...
Mycotoxin occurrence in food worldwide is estimated to increase due climate change. Moreover, studies on how these contaminants interfere with medications and especially anticancer therapies are rare. With the rise of immunotherapies, particularly mycotoxins immunomodulatory activity, such as alternariol (AOH) or deoxynivalenol (DON), great concern. Both pro-inflammatory nuclear factor kappa B (NF-κB) pathway myeloid cells. This not only plays an important role immune response but also...
Abstract Our diet does not only impact our risk for cancer, but might also affect the outcome of anti-cancer therapies. While interaction natural food constituents or supplements with anticancer therapies are frequently investigated, studies on how contaminants, such as mycotoxins, interfere drugs is rare lacking, despite rise mycotoxin occurrence in worldwide. As importance immune system during now well known, especially mycotoxins immunomodulatory activity, alternariol (AOH) deoxynivalenol...