showing 9 related works from this author
Exploring the Chemoselectivity towards Cysteine Arylation by Cyclometallated Au III Compounds: New Mechanistic Insights
2020
To gain more insight into the factors controlling the efficient cysteine arylation by cyclometalated Au(III) complexes, the reaction between selected gold compounds and different peptides was investigated by high‐resolution liquid chromatography electrospray ionization mass spectrometry (HR‐LC‐ESI‐MS). The deducted mechanisms of C–S cross‐coupling, also supported by density functional theory (DFT) and quantum mechanics/molecular mechanics (QM/MM) calculations, evidenced the key role of secondary peptidic gold binding sites in favouring the process of reductive elimination.
Comparative biological evaluation and G-quadruplex interaction studies of two new families of organometallic gold(I) complexes featuring N-heterocycl…
2020
Experimental organometallic gold(I) compounds hold promise for anticancer therapy. This study reports the synthesis of two novel families of gold(I) complexes, including N1-substituted bis-N-heterocyclic carbene (NHC) complexes of general formula [Au(N1-TBM) 2]BF 4 (N1-TBM = N1-substituted 9-methyltheobromin-8-ylidene) and mixed gold(I) NHC-alkynyl complexes, [Au(N1-TBM)alkynyl]. The compounds were fully characterised for their structure and stability in aqueous environment and in the presence of N-acetyl cysteine by nuclear magnetic resonance (NMR) spectroscopy. The structures of bis(1-ethyl-3,7,9-trimethylxanthin-8-ylidene)gold(I), (4-ethynylpyridine)(1,9-dimethyltheobromine-8-ylidene)gol…
Selective targeting of PARP-1 zinc finger recognition domains with Au(III) organometallics
2018
The binding of Au(iii) complexes to the zinc finger domain of the anticancer drug target PARP-1 was studied using a hyphenated mass spectrometry approach combined with quantum mechanics/molecular mechanics (QM/MM) studies. Competition experiments were carried out, whereby each Au complex was exposed to two types of zinc fingers. Notably, the cyclometallated Au-C^N complex was identified as the most selective candidate to disrupt the PARP-1 zinc finger domain, forming distinct adducts compared to the coordination compound Auphen.
Characterization of Hydrophilic Gold(I) N-Heterocyclic Carbene (NHC) Complexes as Potent TrxR Inhibitors Using Biochemical and Mass Spectrometric App…
2017
We report here on the synthesis of a series of mono-and dinuclear gold(I) complexes exhibiting sulfonated bis(NHC) ligands and novel hydroxylated mono(NHC) Au(I) compounds, which were also examined for their 'biological activities. Initial cell viability assays show strong antiproliferative activities of the hydroxylated mono(NHC) gold compounds (8 > 9 > 10) against 2008 human ovarian cancer cells even after 1 h incubation. In order to gain insight into the mechanism of biological action of the gold compounds, their effect on the pivotal cellular target seleno-enzyme thioredoxin reductase (TrxR), involved in the maintenance of intracellular redox balance, was investigated in depth. Th…
The antifibrotic potential of a sustained release formulation of a PDGF beta-receptor targeted rho kinase inhibitor
2019
Rho kinase activity in hepatic stellate cells (HSCs) is associated with activation, transformation and contraction of these cells, leading to extracellular matrix production and portal hypertension in liver cirrhosis. Inhibition of rho kinase activity can reduce these activities, but may also lead to side effects, for instance systemic hypotension. This can be circumvented by liver-specific delivery of a rho kinase inhibitor to effector cells. Therefore, we targeted the rho kinase inhibitor Y27632 to the key pathogenic cells in liver fibrosis, i.e. myofibroblasts including activated HSCs that highly express the PDGF beta-receptor, using the drug carrier pPB-MSA. This carrier consists of mou…
An Organometallic Gold(I) Bis‐N‐Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells
2020
Abstract The organometallic AuI bis‐N‐heterocyclic carbene complex [Au(9‐methylcaffeine‐8‐ylidene)2]+ (AuTMX2) was previously shown to selectively and potently stabilise telomeric DNA G‐quadruplex (G4) structures. This study sheds light on the molecular reactivity and mode of action of AuTMX2 in the cellular context using mass spectrometry‐based methods, including shotgun proteomics in A2780 ovarian cancer cells. In contrast to other metal‐based anticancer agents, this organogold compound is less prone to form coordinative bonds with biological nucleophiles and is expected to exert its drug effects mainly by non‐covalent interactions. Global protein expression changes of treated cancer cell…
CCDC 1913564: Experimental Crystal Structure Determination
2019
Related Article: Samuel M. Meier-Menches, Brech Aikman, Daniel Döllerer, Wim T. Klooster, Simon J. Coles, Nicolò Santi, Louis Luk, Angela Casini, Riccardo Bonsignore|2020|J.Inorg.Biochem.|202|110844|doi:10.1016/j.jinorgbio.2019.110844
CCDC 1916760: Experimental Crystal Structure Determination
2019
Related Article: Samuel M. Meier-Menches, Brech Aikman, Daniel Döllerer, Wim T. Klooster, Simon J. Coles, Nicolò Santi, Louis Luk, Angela Casini, Riccardo Bonsignore|2020|J.Inorg.Biochem.|202|110844|doi:10.1016/j.jinorgbio.2019.110844
CCDC 1940532: Experimental Crystal Structure Determination
2019
Related Article: Samuel M. Meier-Menches, Brech Aikman, Daniel Döllerer, Wim T. Klooster, Simon J. Coles, Nicolò Santi, Louis Luk, Angela Casini, Riccardo Bonsignore|2020|J.Inorg.Biochem.|202|110844|doi:10.1016/j.jinorgbio.2019.110844