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Andrea Kurzwernhart

Bio: Andrea Kurzwernhart is an academic researcher from University of Vienna. The author has contributed to research in topics: Reactivity (chemistry) & Ligand (biochemistry). The author has an hindex of 6, co-authored 8 publications receiving 431 citations.

Papers
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Journal ArticleDOI
TL;DR: Ru(II)(arene)-flavonoids with high in vitro antitumour activity were synthesised and are capable of inhibiting human topoisomerase IIα and binding covalently to DNA.

131 citations

Journal ArticleDOI
TL;DR: Compared to the flavonol ligands, the RuII(η6-p-cymene) complexes are more potent antiproliferative agents, which can be explained by potential multitargeted properties.
Abstract: RuII(arene) complexes have been shown to be promising anticancer agents, capable of overcoming major drawbacks of currently used chemotherapeutics. We have synthesized RuII(η6-arene) compounds carrying bioactive flavonol ligands with the aim to obtain multitargeted anticancer agents. To validate this concept, studies on the mode of action of the complexes were conducted which indicated that they form covalent bonds to DNA, have only minor impact on the cell cycle, but inhibit CDK2 and topoisomerase IIα in vitro. The cytotoxic activity was determined in human cancer cell lines, resulting in very low IC50 values as compared to other RuII(arene) complexes and showing a structure–activity relationship dependent on the substitution pattern of the flavonol ligand. Furthermore, the inhibition of cell growth correlates well with the topoisomerase inhibitory activity. Compared to the flavonol ligands, the RuII(η6-p-cymene) complexes are more potent antiproliferative agents, which can be explained by potential mult...

124 citations

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TL;DR: Recent literature on the use of (thio)pyr(id)ones in bioinorganic chemistry with a focus on their metal ion chelating properties is summarized.

83 citations

Journal ArticleDOI
TL;DR: To expand knowledge about the structure-activity relationships and to determine the impact of lipophilicity of the arene ligand and of the hydrolysis rate on anticancer activity, a series of novel 3-hydroxyflavone derived Ru(II)(η(6)-arene) complexes were synthesised.
Abstract: RuII(η6-arene) complexes, especially with bioactive ligands, are considered to be very promising compounds for anticancer drug design. We have shown recently that RuII(η6-p-cymene) complexes with 3-hydroxyflavone ligands exhibit very high in vitro cytotoxic activities correlating with a strong inhibition of topoisomerase IIα. In order to expand our knowledge about the structure–activity relationships and to determine the impact of lipophilicity of the arene ligand and of the hydrolysis rate on anticancer activity, a series of novel 3-hydroxyflavone derived RuII(η6-arene) complexes were synthesised. Furthermore, the impact of the heteroatom in the bioactive ligand backbone was studied by comparing the cytotoxic activity of RuII(η6-p-cymene) complexes of 3-hydroxyquinolinone ligands with that of their 3-hydroxyflavone analogues. To better understand the behaviour of these RuII complexes in aqueous solution, the stability constants and pKa values for complexes and the corresponding ligands were determined. Furthermore, the interaction with the DNA model 5′-GMP and with a series of amino acids was studied in order to identify potential biological target structures.

72 citations

Journal ArticleDOI
TL;DR: The flavonol scaffold is confirmed as a promising O,O-chelating ligand system for the development of anticancer active organometallics and exhibits in vitro anticancer activities in the high nM to low μM range.
Abstract: Flavonol-derived OsII(cym) and RhIII-Cp* complexes were synthesized and the impact of the metal center on aqueous stability, reactivity toward biomolecules, and cytotoxic activity was compared to RuII analogs. The RhIII complexes were the most stable to ligand release in aqueous solution and showed the highest preference for ubiquitin binding. Investigations on the reactivity toward nucleoside triphosphates revealed the clear affinity of RhIII to 5′-dATP, whereas RuII and OsII prefer binding to 5′-dGTP. Simultaneous incubation with amino acids and nucleoside triphosphates reveals the preference toward amino acids, indicating that binding to proteins might be a key step in the mechanism of action of this compound class. The complexes exhibit in vitro anticancer activities in the high nM to low μM range, confirming the flavonol scaffold as a promising O,O-chelating ligand system for the development of anticancer active organometallics.

22 citations


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01 Jan 2008
TL;DR: The recent achievement of oxaliplatin for the treatment of colon cancer should not belie the imbalance between a plethora of investigated complexes and a very small number of clinically approved platinum drugs.
Abstract: Triggered by the resounding success of cisplatin, the past decades have seen tremendous efforts to produce clinically beneficial analogues. The recent achievement of oxaliplatin for the treatment of colon cancer should, however, not belie the imbalance between a plethora of investigated complexes and a very small number of clinically approved platinum drugs. Strategies opening up new avenues are increasingly being sought using complexes of metals other than platinum such as ruthenium or gallium. Based on the chemical differences between these metals, the spectrum of molecular mechanisms of action and potential indications can be broadened substantially. Other approaches focus on complexes with tumour-targeting properties, thereby maximizing the impact on cancer cells and minimizing the problem of adverse side effects, and complexes with biologically active ligands.

698 citations

Journal ArticleDOI
30 May 1953-Nature
TL;DR: The International Tables for X-ray Crystallography (ITC) as mentioned in this paper were published by the International Union of Crystallographers (IUC) for the first time in 1952.
Abstract: International Tables for X-Ray Crystallography (Published for the International Union of Crystallography.) Vol. 1: Symmetry Groups. Edited by Norman F. M. Henry and Kathleen Lonsdale. Pp. xi + 558. (Birmingham: Kynoch Press, 1952.) 105s.

691 citations

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TL;DR: A detailed account of the latest results of metal-based drugs and their potential uses in the cure of severe diseases is provided and the number of published studies in this field is huge.

560 citations

Journal ArticleDOI
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.

489 citations

Journal ArticleDOI
TL;DR: This review has endeavored to showcase how a "multitargeted" approach to drug design has led to new families of metallodrugs which may not only reduce systemic toxicities associated with modern day chemotherapeutics but also address resistance issues that are plaguing many Chemotherapeutic regimens.
Abstract: While medicinal inorganic chemistry has been practised for over 5000 years, it was not until the late 1800s when Alfred Werner published his ground-breaking research on coordination chemistry that we began to truly understand the nature of the coordination bond and the structures and stereochemistries of metal complexes. We can now readily manipulate and fine-tune their properties. This had led to a multitude of complexes with wide-ranging biomedical applications. This review will focus on the use and potential of metal complexes as important therapeutic agents for the treatment of cancer. With major advances in technologies and a deeper understanding of the human genome, we are now in a strong position to more fully understand carcinogenesis at a molecular level. We can now also rationally design and develop drug molecules that can either selectively enhance or disrupt key biological processes and, in doing so, optimize their therapeutic potential. This has heralded a new era in drug design in which we a...

389 citations