Christian Hartinger

• Prof. Dr.
• Metal-based Anticancer Drug Development at University of Auckland

A novel series of organometallic antitumour agents based on RuII and OsII complexes containing N-substituted 2-pyridinecarbothioamides (PCAs) has been synthesized and characterized. To the best of our knowledge, this is the first report of organometallic anticancer compounds with an S,N-bidentate ligand system. While the ligands showed activity as...

Organometallic Ru(II), Os(II) and Rh(III) complexes of lapachol induce apoptosis in human tumour cell lines in the low μM range by a mode of action involving oxidative stress, especially in the case of the ruthenium compound.

Ru(II)(arene) complexes have been shown to be promising anticancer agents, capable of overcoming major drawbacks of currently used chemotherapeutics. We have synthesized Ru(II)(η(6)-arene) compounds carrying bioactive flavonol ligands with the aim to obtain multi-targeted anticancer agents. In order to validate this concept, studies on the mode of...

Ru(II)(arene)-flavonoids with high in vitro antitumour activity were synthesised. These compounds are capable of inhibiting human topoisomerase IIα and binding covalently to DNA.

Multinuclear platinum anticancer complexes are a proven option to overcome resistance of established anticancer compounds. Transferring this concept to ruthenium complexes led to the synthesis of dinuclear Ru(II)-arene compounds containing a bis(pyridinone)alkane ligand linker. A pronounced influence of the spacer length on the in vitro anticancer...

Piano‐stool complexes of ruthenium and other platinum group metals have shown promising preclinical results as anticancer agents, often with alternative modes of action to traditional platinum‐based compounds. Quinoline is considered a privileged structure in medicinal chemistry and many complexes with potent anticancer activity have been reported....

[M(arene)(HQ)Cl] complexes (M = Ru II /Os II /Rh III /Ir III ; HQ = 8-hydroxyquinoline) have shown promise as anticancer agents. To assess the effect of conjugating biotin (vitamin B7) to such compounds and improve their tumor-targeting...

Some half-sandwich compounds with a variety of ligands and metal centres have shown promising anticancer activity.

Metal piano-stool complexes based on pyridinecarbothioamide (PCA) have shown promising antiproliferative and in vivo anticancer activity, in particular [Ru(cym)(p-F-PCA)Cl]PF6 (cym is η⁶-p-cymene; plecstatin-1). The impact of modifications of the PCA and π-bound ligands on biological properties has been extensively investigated. Herein, we explored...

Heterobimetallic cages built from Pd and either octahedral Ru or square-planar Pt moieties and bridged by ligands with H bonding-accepting or -donating properties are reported. They showed stimulus-responsive dis- and...

Metallosupramolecular architectures formed from metal ions and bridging ligands are increasing in popularity due to their range of applications and ease of self-assembly. Many are able to readily change their...

The clinical use of many potent anticancer agents is limited by their non‐selective toxicity to healthy tissue. One of these examples is vorinostat (SAHA), a pan histone deacetylase inhibitor, which shows high cytotoxicity with limited discrimination for cancerous over healthy cells. In an attempt to improve tumor selectivity, we exploited the prop...

Synthesis and biological activity of two series of modified side chain methotrexate (MTX) derivatives are presented, one with a ferrocenyl moiety inserted between the pteroyl and glutamate portions of the molecule and the other with glutamate substituted for short chain amino acids. Ferrocenyl derivatives of MTX turned out to be rather moderate inh...

Modern approaches in metallodrug research focus on compounds that bind protein targets rather than DNA. However, the identification of protein targets and binding sites is challenging. Using intact mass spectrometry and proteomics, we investigated the binding of the antimetastatic agent RAPTA‐C to the model proteins ubiquitin, cytochrome c, lysozym...

AA dynamic covalent approach was exploited to generate a family of homometallic [PtnL2n]2n+ cage (predominantly [Pt2L4]4+ systems) architectures. The family of platinum(II) architectures were characterized using 1H nuclear magnetic resonance...

Mass spectrometry (MS) is an analytical technique for molecule identification that can be used for investigating protein-metal complex interactions. Once the MS data is collected, the mass spectra are usually interpreted manually to identify the adducts formed as a result of the interactions between proteins and metal-based species. However, with i...

The cellular accumulation and the underlying mechanisms for the two ruthenium-based anticancer complexes [RuII(cym)(HQ)Cl] 1 (cym = η6-p-cymene, HQ = 8-hydroxyquinoline) and [RuII(cym)(PCA)Cl]Cl 2 (PCA = N-fluorophenyl-2-pyridinecarbothioamide) were investigated in HCT116 human colorectal carcinoma cells. The results showed that the cellular accumu...

Mass spectrometry (MS) is an analytical technique for molecule identification that can be used for investigating protein-metal complex interactions. Once the MS data is collected, the mass spectra are usually interpreted manually to identify the adducts formed which arise from the interactions between proteins and metal-based species. However, with...

Mass spectrometry (MS) is an analytical technique for molecule identification that can be used for investigating protein-metal complex interactions. Once the MS data is collected, the mass spectra are usually interpreted manually to identify the adducts formed which arise from the interactions between proteins and metal-based species. However, with...

Ruthenium piano-stool complexes have been explored for their anticancer activity and some promising compounds have been reported. Herein, we conjugated a derivative of plecstatin-1 to peptides in order to increase their cancer cell targeting ability. For this purpose, plecstatin-1 was modified at the arene ligand to introduce a functional amine han...

Intracellular accumulation studies are a key step in metallodrug development but often variable results are obtained. Therefore, we aimed here to investigate different protocols for efficient and reproducible lysis of cancer cells in terms of protein content in lysates and in cell uptake studies of the Ru anticancer complex [chlorido(8-oxyquinolina...

With the aim to combine more than one biologically‐active component in a single molecule, derivatives of ispinesib and its (S) analogue were prepared that featured ferrocenyl moieties or bulky organic substituents. Inspired by the strong kinesin spindle protein (KSP) inhibitory activity of ispinesib, the compounds were investigated for their antipr...

Nanomaterials that mimic the catalytic activity of natural enzymes in the complex biological environment of the human body are called nanozymes. Recently, nanozyme systems have been reported with diagnostic, imaging, and/or therapeutic capabilities. Smart nanozymes strategically exploit the tumor microenvironment (TME) by the in situ generation of...

A new sequential metalation strategy that enables the assembly of a new more robust reduced symmetry heterobimetallic [PdPtL4]4+ cage C is reported. By exploiting a low-symmetry ditopic ligand (L) that features imidazole and pyridine donor units we were able to selectively form a [Pt(L)4]2+ "open-cage" complex. When this was treated with Pd(ii) ion...

Antimitotic agents are among the most important drugs used in anticancer therapy. Kinesin spindle protein (KSP) was proposed as a promising target for new antimitotic drugs. Herein, we report the synthesis of Ru, Os, Rh, and Ir half-sandwich complexes with the KSP inhibitor ispinesib and its (S)-enantiomer. Conjugation of the organometallic moiety...

Half-sandwich MII(cym)Cl (cym = η6-p-cymene; M = Ru, Os) complexes of pyridinecarbothioamide (PCA) ligands have demonstrated potential as orally active anticancer agents. In order to investigate the impact of the substitution of the labile chlorido ligand with phosphorous donor-based ligands on the antiproliferative properties, the triphenylphosphi...

Using ferrocene-based ligand systems, a series of heterobimetallic architectures of the general formula [PdmLn]x+ were designed with the aim of installing an opening and closing mechanism that would allow the release and binding of guest molecules. Palladium complex formation was achieved through coordination to pyridyl groups, and using 2-, 3-, an...

Pt(terpyridine) complexes are well-known as DNA intercalators. The introduction of an NHC co-ligand rendered the complex highly antiproliferative in cancer cells compared to its chlorido derivative. Despite the high potency,...

Half-sandwich MII(cym)Cl (cym = η6-p-cymene; M = Ru, Os) complexes of pyridinecarbothioamide (PCA) ligands have demonstrated potential as orally active anticancer agents. In order to investigate the impact of the substitution of the labile chlorido ligand with phosphorous donor ligands on the antiproliferative properties, the triphenylphosphine (PP...

A new [PdPtL4]4+ heterobimetallic cage containing hydrazone linkages has been synthesised using the sub-component self-assembly approach. 1H and DOSY nuclear magnetic resonance (NMR) spectroscopy and electrospray ionisation mass spectrometry (ESIMS) data were consistent with the formation of the [PdPtL4]4+ architecture. The cage was stimulus-respon...

The substitution of phenyl rings in established drugs with ferrocenyl moieties has been reported to yield compounds with improved biological activity and alternative modes of action, often involving the formation of reactive oxygen species (ROS). Translating this concept to N-heterocyclic carbene (NHC) complexes, we report here organometallics with...

Organometallic Rh(Cp*) (Cp* = η5-pentamethylcyclopentadienyl) complexes with monodentate N-heterocyclic carbene (NHC) ligands bearing a pendant anthracenyl substituent have been shown to undergo intramolecular C-C coupling reactions. Herein, two bidentate NHC ligands substituted with pyridyl or triazolyl donor groups were prepared along with the co...

Metal complexes bind to a wide variety of biomolecules and the control of the reactivity is essential when designing anticancer metallodrugs with a specific mode of action in mind. In this study, we used the highly cytotoxic compound [RuII(cym)(8-HQ)Cl] (cym = η6-p-cymene, 8-HQ = 8-hydroxyquinoline), the more inert derivative [RuII(cym)(8-HQ)(PTA)]...

A strategy for the generation of heterotrimetallic double cavity (DC) cages [PdnPtmL4]⁶⁺ (DC1: n=1, m=2; and DC2: n=2, m=1) is reported. The DC cages were generated by combining an inert platinum(II) tetrapyridylaldehyde complex with a suitably substituted pyridylamine and PdII ions. ¹H and DOSY nuclear magnetic resonance spectroscopy (NMR) and ele...

The functionalization of Ru(arene) complexes with bioactive moieties is a promising approach for modulating their biological properties. This strategy may result in compounds with synergistic biological effects which may be capable of overcoming major drawbacks of currently used chemotherapeutics. A series of RuII(η⁶-p-cymene)Cl complexes 1a–1c com...

The number of donor atoms available on peptides that can competitively coordinate to metal centers renders the site‐selective generation of advanced metal‐peptide conjugates in high purity a challenging venture. Herein, we present a transmetalation‐based synthetic approach on solid support in which an imidazolium pro‐ligand can be used to selective...

A strategy for the generation of heterotrimetallic double cavity (DC) cages [PdnPtmL4]6+ (DC1: n = 1, m = 2; and DC2: n = 2, m = 1) is reported. The DC cages were generated by combining an inert platinum(II) tetrapyridylaldehyde complex with a suitably substituted pyridylamine and Pd(II) ions. 1H and DOSY nuclear magnetic resonance spectroscopy (NM...

Redox‐active Cu(II) complexes are able to form reactive oxygen species (ROS) in the presence of oxygen and reducing agents. Recently, Faller et al. reported that ROS generation by Cu(II) ATCUN complexes is not as high as assumed for decades. High complex stability results in silencing of the Cu(II)/Cu(I) redox cycle and therefore leads to low ROS g...

Multimetallic complexes have been shown in several examples to possess greater anticancer activity than their monometallic counterparts. The increased activity has been attributed to altered modes of action. We herein report the synthesis of a series of heterodimetallic compounds based on a ditopic ligand featuring 2-pyridylimine chelating motifs a...

The incorporation of the ferrocenyl moiety into a bioactive molecule may significantly alter the activity of the resulting conjugate. By applying this strategy, we designed ferrocenyl analogs of monastrol – the first low molecular weight kinesin spindle protein (KSP) inhibitor. The obtained compounds showed low micromolar antiproliferative activity...

Understanding binding site preferences in biological systems as well as affinities to binding partners is a crucial aspect in metallodrug development. We here present a mass spectrometry‐based method to compare relative stabilities of metal‐peptide adducts in the gas phase. Angiotensin 1 and substance P were used as model peptides. Incubation with...

Metastatic castration-resistant prostate cancer (CRPC) has a five-year survival rate of 28%. As histone deacetylases (HDACs) are overexpressed in CRPC, the HDAC inhibitor suberoylanilide hydroxamic acid (SAHA) was trialled in CRPC patients but found to be toxic and inefficacious. Previously, we showed that novel HDAC inhibitors (Jazz90 (N1-hydroxy-...

In-flow small angle X-ray scattering (SAXS) was used to probe in real-time (typically every second) the hydrolysis of whey protein isolate (WPI) by bromelain. The WPI concentration was 2.5%, the enzyme to substrate ratio was 1:10, and the enzymatic reaction was followed for 90 min at 50°C and pH 7. SAXS showed that the average size of WPI molecules...

We report investigations on the anticancer activity of organometallic [MII/III(η⁶‐p‐cymene/η⁵‐pentamethylcyclopentadienyl)] (M=Ru, Os, Rh, and Ir) complexes of N‐heterocyclic carbenes (NHCs) substituted with a triazolyl moiety. Depending on the precursors, the NHC ligands displayed either mono‐ or bidentate coordination via the NHC carbon atom or a...

Metal complexes can be considered a “paradigm of promiscuity” when it comes to their interactions with proteins. They often form adducts with a variety of donor atoms in an unselective manner. We have characterized the adducts formed between a series of isostructural N‐heterocyclic carbene (NHC) complexes with Ru, Os, Rh, and Ir centers and the mod...

Two new di(2,2′-bipyridine) ligands, 2,6-bis([2,2′-bipyridin]-5-ylethynyl)pyridine (L1) and bis(4-([2,2′-bipyridin]-5-ylethynyl)phenyl)methane (L2) were synthesized and used to generate two metallosupramolecular [Fe2(L)3](BF4)4 cylinders. The ligands and cylinders were characterized using elemental analysis, electrospray ionization mass spectrometr...

Metallodrugs have a central role in the treatment and diagnosis of diseases. To overcome potential toxicity and equip metal-based anticancer agents with biological activity, the choice of the ligands coordinated to the metal center is essential. A recent strategy to address the shortcomings of current drugs and improve their targeted properties, is...

Isostructural N-heterocyclic carbene Ru, Os, Rh, and Ir complexes showed distinctive reactivity to hen egg white lysozyme by forming adducts at different binding sites and/or underwent different ligand exchange reactions. Protein crystallography, mass spectrometry and computational studies demonstrated the role of the metal centers and the protein...

Carbon monoxide (CO) is an endogenously produced gasotransmitter that is involved in a range of physiological roles including the stabilisation of hypoxia‐inducible factor (HIF), a transcription factor that regulates oxygen homeostasis. Herein, by using CO‐releasing molecule‐2 as a CO donor, we show that CO is an inhibitor of HIF PHD2, one of the m...

Increasingly explored over the last decade, gold complexes have shown great promise in the field of cancer therapeutics. A major obstacle to their clinical progression has been their lack of in vivo stability, particularly for gold(III) complexes, which often undergo facile reduction in the presence of biomolecules such as glutathione. Herein, we r...

This review highlights the progress in the development of ruthenium(II)/(III) complexes with flavone derivatives as potential therapeutic agents. We focused on natural hydroxyflavone derivatives and their synthetic amino analogues as ligands in ruthenium(II)/(III) complexes which demonstrate antimicrobial, antitumor activity and/or enzyme inhibitio...

The small molecule anticancer agent cisplatin and its Pt(II) analogs carboplatin and oxaliplatin are widely used to treat a variety of tumorigenic diseases. Despite their structural simplicity, side effects and disadvantages, they are cornerstones of cancer chemotherapy. Several strategies have been pursued to enhance the activity and reduce the si...

Ruthenium-based complexes have attracted attention as promising anticancer candidates due to their lower general toxicity than the widely used platinum drugs. The complex [RuII(η6-p-cymene)(8-oxyquinolinato)Cl] 1 has shown significant cytotoxic activity in cancer cells, independent of the cellular uptake. In an attempt to rationalize this finding,...

RuII(cym)Cl (cym = η⁶-p-cymene) complexes of pyridinecarbothioamides have shown potential for development as orally active anticancer metallodrugs, underlined by their high selectivity towards plectin as the molecular target. In order to investigate the impact of the metal center on the anticancer activity and their physicochemical properties, the...

Androgen receptor (AR)-null prostate tumors have been observed in 11–24% of patients. Histone deacetylases (HDACs) are overexpressed in prostate tumors. Therefore, HDAC inhibitors (Jazz90 and Jazz167) were examined in AR-null prostate cancer cell lines (PC3 and DU145). Both Jazz90 and Jazz167 inhibited the growth of PC3 and DU145 cells. Jazz90 and...

Hydroxypyr(id)ones are a pharmaceutically important class of compounds that have shown potential in diverse areas of drug discovery. We investigated the 3-hydroxy-4-pyridones 1a–1c and 3-hydroxy-4-thiopyridones 1d–1f as well as their Ru(η6-p-cymene)Cl complexes 2a–2f, and report here the molecular structures of 1b and 1d as determined by X-ray diff...

The development of bifunctional platinum complexes with the ability to interact with DNA via different binding modes is of interest in anticancer metallodrug research. Therefore, we report platinum(II) terpyridine complexes to target DNA by coordination and/or through a tethered alkylating moiety. The platinum complexes were evaluated for their in...

In some instances, multimetallic complexes have shown higher anticancer activity than mononuclear analogues, possibly by interacting with target molecules through a different binding mode. Therefore, a series of novel bis-pyridylimine-based homodinuclear MII/III(cym/Cp*)Cl (cym = η⁶-p-cymene: M = Ru, Os; Cp* = pentamethylcyclopentadienyl: M = Rh, I...

While most Rh-N-heterocyclic carbene (NHC) complexes currently investigated in anticancer research contain a Rh(III) metal center, an increasing amount of research is focusing on the cytotoxic activity and mode of action of square-planar [RhCl(COD)(NHC)] (where COD = 1,5-cyclooctadiene) which contains a Rh(I) center. The enzyme thioredoxin reductas...

Proteomics has played an important role in elucidating the fundamental processes occuring in living cells. Translating these methods to metallodrug research ('metalloproteomics') has provided a means for molecular target identification of metal-based anticancer agents which should signifcantly advance the research field. In combination with biologi...

Ispinesib is a potent inhibitor of kinesin spindle protein (KSP), which has been identified as a promising target for antimitotic anticancer drugs. Herein, we report the synthesis of half-sandwich complexes of Ru, Os, Rh, and Ir bearing the ispinesib-derived N,N-bidentate ligands (R)- and (S)-2-(1-amino-2-methylpropyl)-3-benzyl-7-chloroquinazolin-4...

Thiones have been investigated as ligands in metal complexes with catalytic and biological activity. We report the synthesis, characterization, and biological evaluation of a series of MII/III complexes of the general formulae [MII(cym)(L)Cl]X (cym = η⁶-p-cymene) or [MIII(Cp*)(L)Cl]X (Cp* = η⁵-pentamethylcyclopentadienyl), where X = Cl⁻ or PF6⁻, an...

The combination of more than one bioactive moiety in a multitargeted anticancer agent may result in synergistic activity of its components. Using this concept, bioorganometallic compounds were designed to feature a metal center, a 2‐pyridinecarbothioamide (PCA), and a hydroxamic acid, which is found in the anticancer drug vorinostat (SAHA). The org...

Creating synergies: The combination of more than one bioactive moiety resulted in an organometallic compound featuring a metal center, a 2‐pyridinecarbothioamide (PCA), and a hydroxamic acid, which is found in the anticancer drug vorinostat (SAHA). The compound displayed different modes of action than its components, supporting the development of n...

A strategy is presented that enables the quantitative assembly of a heterobimetallic [PdPtL4]⁴⁺ cage. The presence of two different metal ions (PdII and PtII) with differing labilities enables the cage to be opened and closed selectively at one end upon treatment with suitable stimuli. Combining an inert PtII tetrapyridylaldehyde complex with a sui...

As part of efforts to enhance the applications of self‐assembled metallosupramolecular architectures (MSAs) there is considerable current interest in the development of lower symmetry heterometallic systems. Herein we report a strategy that enables the quantitative assembly of low symmetry heterobimetallic [PdPtL 4 ] 4+ cage C. We anticipated that...

Metal complexes provide a versatile platform to develop novel anticancer pharmacophores, and they form stable compounds with N-heterocyclic carbene (NHC) ligands, some of which have been shown to inhibit the cancer-related selenoenzyme thioredoxin reductase (TrxR). To expand a library of isostructural NHC complexes, we report here the preparation o...

The syntheses and characterisation of the complexes [Co(pmea)(O2SO2)]ClO4 and [Co(pmap)(O2SO2)]ClO4 (pmea = bis((2-pyridyl)methyl)-2-((2-pyridyl)ethyl)amine; pmap = bis(2-(2-pyridyl)ethyl)(2-pyridylmethyl)amine), containing chelating sulfato ligands, are reported. These were prepared by oxidation of a solution containing CoSO4·7H2O and the tripodal...

The scientific interest in cadmium (Cd) as a human health damaging agent has significantly increased over the past decades. However, particularly the histological distribution of Cd in human tissues is still scarcely defined. Using inductively coupled plasma-mass spectrometry (ICP-MS), we determined the concentration of Cd in 40 different human tis...

Redox-modulating anticancer drugs allow the exploitation of altered redox biology observed in many cancer cells. We discovered dinuclear Rh III (Cp*) and Ir III (Cp*) complexes that have in vitro anticancer activity superior to...

Organometallic compounds based on bioactive ligand systems have shown promising antiproliferative properties. The use of 8-hydroxyquinoline and its derivatives as bioactive ligands resulted in organometallic complexes with potent anticancer activity, but they lack aqueous solubility for further development. We report here the preparation of a serie...

Cisplatin and its second and third generation analogues are widely used in the treatment of cancer. To study their reactions with proteins, we present a method based on SDS‐PAGE separation and laser ablation–inductively coupled plasma‐mass spectrometry (LA–ICP‐MS) for platinum detection in the reaction between human serum albumin (HSA) and cisplati...

In recent years, extensive research efforts have been focused on loading metal complexes onto macromolecular systems such as nanoparticles. We report a ligand with a catechol group based on a picolinamide which allows for coordination to organoruthenium moieties while the catechol group remains available for loading on nanoparticles as delivery veh...

The stoichiometry and stability constants of the gallium(III) and iron(III) complexes of two alkoxycarbonylmethyl-3-hydroxy-2(1H)-pyridinone ligands were determined by means of pH-potentiometry, UV–Vis spectrophotometry and ¹H and ⁷¹Ga NMR spectroscopy in aqueous solution. The cytotoxicity of one of the gallium(III) complexes was also measured in m...

Benzoylthiourea derivatives feature several donor atoms capable of coordinating to metal centers. We report here a series of Ru(η⁶‐p‐cymene) complexes employing benzoylthiourea derivatives as ligands. Such ligands often coordinate to metal centers through their S and O donor atoms. We isolated complexes where the ligands were mono‐ or bidentately c...

Correction for ‘Unexpected arene ligand exchange results in the oxidation of an organoruthenium anticancer agent: the first X-ray structure of a protein–Ru(carbene) adduct’ by Matthew P. Sullivan et al. , Chem. Commun. , 2018, 54 , 6120–6123.

Nonsteroidal antiinflammatory drugs (NSAIDs) have chemopreventive effects in several cancer types, and the oxicam-based NSAIDs meloxicam and piroxicam exhibit potential to treat cancer. We prepared a series of novel oxicams and coordinated them to RuII(cym)Cl and OsII(cym)Cl moieties (η⁶-p-cymene = cym). The oxicam ligands acted either as monodenta...

The promise of the metal(arene) structure as an anticancer pharmacophore has prompted intensive exploration of this chemical space. While N-heterocyclic carbene (NHC) ligands are widely used in catalysis, they have only recently been considered in metal complexes for medicinal applications. Surprisingly, a comparatively small number of studies have...

Chalcones and 1,2-benzothiazines are two important classes of bioactive compounds, each scaffold endowed with diverse pharmacological activities. Combining both of these pharmacophores in a single molecule was aimed to yield multi-modal agents. Herein, we report a series of hybrid compounds 3a–3o derived from chalcones and 1,2-benzothiazine cores....

Size-exclusion chromatography–inductively coupled plasma–mass spectrometry (SEC–ICP–MS) was used to study the serum-binding preferences of two metallodrugs with anticancer activities in vivo, namely the organoruthenium compound plecstatin-1 and its isosteric osmium analog. The complexes were administered intraperitoneally into mice bearing a CT-26...

The dinuclear anticancer agents 1,n-bis{chlorido[3-(oxo-κO)-2-methyl-4-(1H)-pyridinonato-κO4](η⁶-p-cymene)-ruthenium(II)}alkane (PyRu 2ⁿ) exhibit high antiproliferative activity in human cancer cell. Reactivity studies with DNA and protein revealed uncommon protein–DNA and DNA–DNA crosslinking ability. We report here studies on the reactions of the...

RuII(η6-arene) compounds carrying bioactive flavonol ligands have shown promising anticancer activity against tumor cells via a multitargeting mode of action, i.e., through interaction with DNA and inhibition of topoisomerase IIα. By introducing a novel arene ligand based on the amino acid l-phenylalanine (Phe), we aimed to alter the pharmacologica...

Anticancer active RuII(η6‐p‐cymene) complexes of bioactive 2‐pyridinecarbothioamide ligands (PCAs) were shown to have high selectivity for plectin and can be administered orally (Chem. Sci., 2013, 4, 1837‐1846 and Angew. Chem. Int. Ed., 2017, 56, 8267 ‐8271). Herein, we report the functionalization of the PCA ligand with a sulfonamide functional gr...