Publications by authors named "Dominik Wenisch"

5 Publications

  • Page 1 of 1

Tridentate 3-Substituted Naphthoquinone Ruthenium Arene Complexes: Synthesis, Characterization, Aqueous Behavior, and Theoretical and Biological Studies.

Inorg Chem 2021 Jun 11. Epub 2021 Jun 11.

Faculty of Chemistry, Institute of Inorganic Chemistry, University of Vienna, Waehringer Str. 42, 1090 Vienna, Austria.

A series of nine Ru arene complexes bearing tridentate naphthoquinone-based ,,-ligands was synthesized and characterized. Aqueous stability and their hydrolysis mechanism were investigated via UV/vis photometry, HPLC-MS, and density functional theory calculations. Substituents with a positive inductive effect improved their stability at physiological pH (7.4) intensely, whereas substituents such as halogens accelerated hydrolysis and formation of dimeric pyrazolate and hydroxido bridged dimers. The observed cytotoxic profile is unusual, as complexes exhibited much higher cytotoxicity in SW480 colon cancer cells than in the broadly chemo- (incl. platinum-) sensitive CH1/PA-1 teratocarcinoma cells. This activity pattern as well as reduced or slightly enhanced ROS generation and the lack of DNA interactions indicate a mode of action different from established or previously investigated classes of metallodrugs.
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http://dx.doi.org/10.1021/acs.inorgchem.1c01083DOI Listing
June 2021

Complex formation of an estrone-salicylaldehyde semicarbazone hybrid with copper(II) and gallium(III): Solution equilibria and biological activity.

J Inorg Biochem 2021 Jul 24;220:111468. Epub 2021 Apr 24.

Department of Inorganic and Analytical Chemistry, Interdisciplinary Excellence Centre, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary; MTA-SZTE Lendület Functional Metal Complexes Research Group, University of Szeged, Dóm tér 7, H-6720 Szeged, Hungary.

The solution chemical properties such as proton dissociation, complex formation with copper(II) and gallium(III) ions in addition to antibacterial and antitumor activity of a novel tridentate salicyaldehyde semicarbazone-estrone hybrid (estrone-SC) and a related bicyclic compound (thn-SC) were investigated. The crystal structure of complex [Cu(thn-SCH)Cl] was studied by single crystal X-ray diffraction method. Estrone-SC and thn-SC form mono-ligand complexes with Cu(II) characterized by relatively high stability, however, they are much less stable than their thiosemicarbazone analogues. The neutral Cu(II) complexes with (O,N,O)(HO) coordination mode predominate at physiological pH. Estrone-SC and thn-SC are more efficient Ga(III) binders in comparison with thiosemicarbazones, although the complexes also suffer dissociation at pH 7.4. The Cu(II) complex of estrone-SC displayed significant cytotoxicity in A549, SW480 and CH1/PA cancer cells, and moderate apoptosis induction and ROS formation. The semicarbazone compounds did not exhibit antibacterial effect; unlike the related Cu(II)-thiosemicarbazone complexes represented by the fairly low MIC values (3-50 μM) obtained on the Gram-positive Staphylococcus aureus and Enterococcus faecalis bacteria.
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http://dx.doi.org/10.1016/j.jinorgbio.2021.111468DOI Listing
July 2021

Highly Aromatic Flavan-3-ol Derivatives from Palaeotropical Buch.-Ham Possess Radical Scavenging and Antiproliferative Properties.

Molecules 2021 Feb 18;26(4). Epub 2021 Feb 18.

Department of Botany and Biodiversity Research, Faculty of Life Science, University of Vienna, Rennweg 14, A-1030 Vienna, Austria.

Phytochemical investigation of leaves and stembark of collected in Thailand resulted in three yet undescribed isomeric flavan-3-ol derivatives (-), the four known compounds gambircatechol (), (+)-catechin (), (+)-afzelechin () and the stilbene oxyresveratrol (). Compounds to feature 6/6/5/6/5/6 core structures. All structures were deduced by NMR and MS, while density functional theory (DFT) calculations on B3LYP theory level were performed of compounds to to support the stereochemistry in positions 2 and 3 in the C-ring. Possible biosynthetic pathways leading to are discussed. The DPPH assay revealed high radical scavenging activities for (EC = 9.4 ± 1.0 µmol mL), (12.2 ± 1.1), (10.0 ± 1.5) and (19.0 ± 2.6), remarkably lower than ascorbic acid (EC = 34.9) and α-tocopherol (EC = 48.6). A cytotoxicity assay revealed moderate but consistent antiproliferative properties of in CH1/PA-1 (ovarian teratocarcinoma) and SW480 (colon carcinoma) cells, with IC values of 25 ± 6 and 34 ± 4 µM, respectively, whereas effects in A549 (non-small cell lung cancer) cells were rather negligible. The performed DCFH-DA assay of in the former cell lines confirmed potent antioxidative effects even in the cellular environment.
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http://dx.doi.org/10.3390/molecules26041078DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7922997PMC
February 2021

Plecstatin-1 induces an immunogenic cell death signature in colorectal tumour spheroids.

Metallomics 2020 12;12(12):2121-2133

Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Währinger Straße 42, 1090, Vienna, Austria.

Organometallic metal(arene) anticancer agents were believed to confer low selectivity for potential cellular targets. However, the ruthenium(arene) pyridinecarbothioamide (plecstatin-1) showed target selectivity for plectin, a scaffold protein and cytolinker. We employed a three-dimensional cancer spheroid model and showed that plecstatin-1 limited spheroid growth, induced changes in the morphology and in the architecture of tumour spheroids by disrupting the cytoskeletal organization. Additionally, we demonstrated that plecstatin-1 induced oxidative stress, followed by the induction of an immunogenic cell death signature through phosphorylation of eIF2α, exposure of calreticulin, HSP90 and HSP70 on the cell membrane and secretion of ATP followed by release of high mobility group box-1.
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http://dx.doi.org/10.1039/d0mt00227eDOI Listing
December 2020

Introducing -, -, and -donor leaving groups: an investigation of the chemical and biological properties of ruthenium, rhodium and iridium thiopyridone piano stool complexes.

Dalton Trans 2020 Nov;49(44):15693-15711

Institute of Inorganic Chemistry, Faculty of Chemistry, University of Vienna, Waehringer Strasse 42, 1090 Vienna, Austria. and Research Cluster "Translational Cancer Therapy Research", Waehringer Strasse 42, 1090 Vienna, Austria.

A series of 15 piano-stool complexes featuring either a RuII, RhIII or IrIII metal center, a bidentate thiopyridone ligand, and different leaving groups was synthesized. The leaving groups were selected in order to cover a broad range of different donor atoms. Thus, 1-methylimidazole served as a N-donor, 1,3,5-triaza-7-phosphaadamantane (pta) as a P-donor, and thiourea as a S-donor. Additionally, three complexes featuring different halido leaving groups (Cl, Br, I) were added. Leaving group alterations were carried out with respect to a possible influence on pharmacokinetic and pharmacodynamic parameters, as well as the cytotoxicity of the respective compounds. The complexes were characterized via NMR spectroscopy, X-ray diffraction (where possible), mass spectrometry, and elemental analysis. Cytotoxicity was assessed in 2D cultures of human cancer cell lines by microculture and clonogenic assays as well as in multicellular tumor spheroids. Furthermore, cellular accumulation studies, flow-cytometric apoptosis and ROS assays, DNA plasmid assays, and laser ablation ICP-MS studies for analyzing the distribution in sections of multicellular tumor spheroids were conducted. This work demonstrates the importance of investigating each piano-stool complexes' properties, as the most promising candidates showed advantages over each other in certain tests/assays. Thus, it was not possible to single out one lead compound, but rather a group of complexes with enhanced cytotoxicity and activity.
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http://dx.doi.org/10.1039/d0dt03165hDOI Listing
November 2020