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pmid:32902006

An Organometallic Gold(I) Bis-N-Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells.

Samuel M Meier-Menches · Benjamin Neuditschko · Katja Zappe · Martin Schaier · Marlene C Gerner · Klaus G Schmetterer · Giorgia Del Favero · Riccardo Bonsignore · Margit Cichna-Markl · Gunda Koellensperger · Angela Casini · Christopher Gerner

Chemistry (Weinheim an der Bergstrasse, Germany) · 2020 doi:10.1002/chem.202003495

Paper

complete

Experiment

complete

Data

partial

Analysis

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Execution

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title
An Organometallic Gold(I) Bis-N-Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells.
doi
10.1002/chem.202003495
pmid
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Samuel M Meier-Menches
[1]
Benjamin Neuditschko
[2]
Katja Zappe
[3]
Martin Schaier
[4]
Marlene C Gerner
[5]
Klaus G Schmetterer
[6]
Giorgia Del Favero
[7]
Riccardo Bonsignore
[8]
Margit Cichna-Markl
[9]
Gunda Koellensperger
[10]
Angela Casini
[11]
Christopher Gerner
journal
Chemistry (Weinheim an der Bergstrasse, Germany)
year
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 cells revealed a multimodal mode of action of AuTMX2 by alterations in the nucleolus, telomeres, actin stress-fibres and stress-responses, which were further supported by pharmacological assays, fluorescence microscopy and cellular accumulation experiments. Proteomic data are available via ProteomeXchange with identifier PXD020560.
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An organometallic gold(I) bis-N-heterocyclic carbene complex with a multimodal mode of action in ovarian cancer cells
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automated cell counter (Moxi Z, Orflo, USA). Viability assay: The MTT assay was used to investigate the c
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