Publications de Christian Hartinger

Understanding the interactions of diruthenium anticancer agents with amino acids

Paul Joseph Dyson, Christian Hartinger, Alexey Nazarov, Muhammad Hanif

The dinuclear anticancer agents 1,n-bis{chlorido3-(oxo-kappa O)-2-methyl-4-(1H)-pyridinonato-kappa O4-ruthenium(II)}alkane (PyRu2n) exhibit high antiproliferative activity in human cancer cell. Reactivity studies with DNA and protein rev ...

SPRINGER2018

The development of RAPTA compounds for the treatment of tumors

Paul Joseph Dyson, Christian Hartinger, Benjamin Samuel Murray

Ruthenium(II)-arene RAPTA-type compounds have been extensively explored for their medicinal properties. Herein a comprehensive review of this class of compounds is provided. A discussion of the basic RAPTA structure is given together with the ways it has b ...

Elsevier Science Sa2016

Target profiling of an antimetastatic RAPTA agent by chemical proteomics: relevance to the mode of action

Paul Joseph Dyson, Christian Hartinger

The clinical development of anticancer metallodrugs is often hindered by the elusive nature of their molecular targets. To identify the molecular targets of an antimetastatic ruthenium organometallic complex based on 1,3,5-triaza-7-phosphaadamantane (RAPTA ...

2015

Protein ruthenation and DNA alkylation: chlorambucil-functionalized RAPTA complexes and their anticancer activity

Paul Joseph Dyson, Christian Hartinger, Alexey Nazarov, Olivier Pierre Zava

Chemotherapeutics for the treatment of tumorigenic conditions that feature novel modes of action are highly sought after to overcome the limitations of current chemotherapies. Herein, we report the conjugation of the alkylating agent chlorambucil to the RA ...

2015

Opening the lid on piano-stool complexes: An account of ruthenium(II)-arene complexes with medicinal applications

Paul Joseph Dyson, Christian Hartinger, Alexey Nazarov

Interest in the medicinal properties of ruthenium(II)-arene compounds has grown rapidly over the last decade. In this account we describe the origins of the field and subsequently highlight developments in the field, including the design of compounds that ...

Elsevier Science Sa2014

Application of mass spectrometric techniques to delineate the modes-of-action of anticancer metallodrugs

Paul Joseph Dyson, Christian Hartinger, Angela Casini, Michael Groessl

Mass spectrometry (MS) has emerged as an important tool for studying anticancer metallodrugs in complex biological samples and for characterising their interactions with biomolecules and potential targets on a molecular level. The exact modes-of-action of ...

Royal Society of Chemistry2013

A new target for gold(I) compounds: glutathione-S.transferase inhibition by auranofin

Paul Joseph Dyson, Christian Hartinger, Angela Casini

Nowadays, gold compounds occupy a relevant position constituting a promising class of experimental anticancer metallodrugs. Several research efforts have been devoted to the investigations of the pharmacological properties of gold(I) complexes bearing phos ...

Elsevier Science Inc2013

Fragmentation methods on the balance: unambiguous top–down mass spectrometric characterization of oxaliplatin–ubiquitin binding sites

Paul Joseph Dyson, Yury Tsybin, Christian Hartinger

The interaction between oxaliplatin and the model protein ubiquitin (Ub) was investigated in a top-down approach by means of high-resolution electrospray ionization mass spectrometry (ESI-MS) using diverse tandem mass spectrometric (MS/MS) techniques, incl ...

Springer-Verlag2012

Anthracene-Tethered Ruthenium(II) Arene Complexes as Tools To Visualize the Cellular Localization of Putative Organometallic Anticancer Compounds

Rosario Scopelliti, Paul Joseph Dyson, Wee Han Ang, Julie Risse, Christian Hartinger, Alexey Nazarov, Michael Groessl, Olivier Pierre Zava, Albert Ruggi, Frédéric Schmitt

Anthracene derivatives of ruthenium(II) arene compounds with 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane (pta) or a sugar phosphite ligand, viz., 3,5,6-bicyclophosphite1,2-O-isopropylidene-alpha-D-glucofuranoside, were prepared in order to evaluate their ...

2012

Synthesis of [Ru-II(eta(6)-p-cymene)(PPh3)(L)Cl]PF6 complexes with carbohydrate-derived phosphites, imidazole or indazole co-ligands

Christian Hartinger, Alexey Nazarov, Muhammad Hanif

Ru-II(arene) complexes of the general formula [Ru-II(eta(6)-p-cymene)(PPh3)(L)Cl]PF6 with L = P- or N-donor systems have been synthesized and characterized. Carbohydrate-derived phosphites, imidazole or indazole have been chosen as co-ligands and different ...

Elsevier2012

Challenges and Opportunities in the Development of Organometallic Anticancer Drugs

Paul Joseph Dyson, Christian Hartinger

This review provides an introduction into the fascinating area of organometallic anticancer compounds. Although the subject dates back many years, it has witnessed considerable growth only in the past decade. A brief overview of the subject together with r ...

Amer Chemical Soc2012

Maleimide-functionalised organoruthenium anticancer agents and their binding to thiol-containing biomolecules

Paul Joseph Dyson, Yury Tsybin, Christian Hartinger, Alexey Nazarov, Michael Groessl, Muhammad Hanif

Ru-II(arene) anticancer compounds with maleimide functionality were prepared to allow selective interaction with thiol-containing biomolecules and thereby enforcing the selective delivery of the compounds to the tumour. ...

Royal Society of Chemistry2012

Polynuclear Ruthenium, Osmium and Gold Complexes. The Quest for Innovative Anticancer Chemotherapeutics

Andrew Douglas Phillips, Christian Hartinger, Alexey Nazarov

Polynuclear compounds are a relatively new and successful approach in metal-based cancer chemotherapy as typified by the trinuclear Pt compound BBR3464 which was evaluated in clinical trials. In this review, we discuss newer developments of polynuclear rut ...

2011

A Ruthenium Antimetastasis Agent Forms Specific Histone Protein Adducts in the Nucleosome Core

Paul Joseph Dyson, Christian Hartinger, Michael Groessl

2011

Metabolization of [Ru(η6-C6H5CF3)(pta)Cl2]: a cytotoxic RAPTA-type complex with a strongly electron withdrawing arene ligand

Paul Joseph Dyson, Anna Katherine Renfrew, Christian Hartinger

The anticancer ruthenium-arene compd. [Ru(η6-C6H5CF3)(pta)Cl2] (pta = 1,3,5-triaza-7-phosphatricyclo[3.3.1.1]decane), termed RAPTA-CF3, with the electron-withdrawing α,α,α-trifluorotoluene ligand, is one of the most cytotoxic RAPTA compds. known. To ration ...

Springer-Verlag2010

An Internal Fluorescent Probe Based on Anthracene to Evaluate Cation-Anion Interactions in Imidazolium Salts

Rosario Scopelliti, Paul Joseph Dyson, Zhaofu Fei, Wee Han Ang, Christian Hartinger, Xuemei Yang

A series of fluorescent imidazolium-based salts contg. the cation [AnCH2MeIm]+ (in which An=anthracene and Im=the imidazolium cation) with Cl-, BF4-, PF6-, SO3CF3-, [N(CN)2]-, [N(SO2CF3)2]-, or PhBF3- anions have been prepd. and characterized. X-ray diffra ...

2010

{(1R,2R,4R)-4-Methyl-1,2-cyclohexanediamine}oxalatoplatinum(II): A Novel Enantiomerically Pure Oxaliplatin Derivative Showing Improved Anticancer Activity in Vivo

Christian Hartinger, Alexey Nazarov

Novel derivatives of the clinically established anticancer drug oxaliplatin were synthesized. Cytotoxicity of the compounds was studied in six human cancer cell lines by means of the MTT assay. Additionally, most promising complexes were also investigated ...

2010

Organometallic antitumour agents with alternative modes of action

Paul Joseph Dyson, Christian Hartinger, Alexey Nazarov, Angela Casini

The therapeutic index of drugs that target DNA, a ubiquitous target present in nearly all cells, is low. Nevertheless, DNA has remained the primary target for medicinal chemists developing metal-based anticancer drugs, although DNA has been essentially aba ...

2010

Ruthenium versus platinum: interactions of anticancer metallodrugs with duplex oligonucleotides characterised by electrospray ionisation mass spectrometry

Paul Joseph Dyson, Yury Tsybin, Christian Hartinger, Michael Groessl

The binding of the ruthenium-based anticancer drug candidates KP1019, NAMI-A and RAPTA-T towards different double-stranded oligonucleotides was probed by electrospray ionisation mass spectrometry and compared with that of the widely used platinum-based che ...

Springer-Verlag2010

Mannich products of kojic acid and N-heterocycles and their Ru(II)-arene complexes: Synthesis, characterization and stability

Paul Joseph Dyson, Christian Hartinger, Alexey Nazarov

Ru(II)-η6-p-cymene compds. bearing pyrone-derived ligands, which were obtained by Mannich reactions between kojic acid and piperidine or morpholine analogs, have been synthesized. The compds. were characterized by NMR spectroscopy, mass spectrometry, therm ...

Elsevier2010