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An Organometallic Gold(I) Bis‐N‐Heterocyclic Carbene Complex with Multimodal Activity in Ovarian Cancer Cells
Author(s) -
MeierMenches Samuel M.,
Neuditschko Benjamin,
Zappe Katja,
Schaier Martin,
Gerner Marlene C.,
Schmetterer Klaus G.,
Del Favero Giorgia,
Bonsignore Riccardo,
CichnaMarkl Margit,
Koellensperger Gunda,
Casini Angela,
Gerner Christopher
Publication year - 2020
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.202003495
Subject(s) - carbene , chemistry , context (archaeology) , mode of action , cancer cell , proteomics , telomere , biophysics , biochemistry , computational biology , combinatorial chemistry , cancer , dna , biology , gene , genetics , paleontology , catalysis
The organometallic Au I bis‐N‐heterocyclic carbene complex [Au(9‐methylcaffeine‐8‐ylidene) 2 ] + ( AuTMX 2 ) 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 AuTMX 2 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 AuTMX 2 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.