Fluorinated N‑heterocyclic carbene silver(I) complexes with high cancer cell selectivity

King, Oliver S., Hofmann, Benjamin J. ORCID: https://orcid.org/0000-0001-6408-3472, Boakye-Smith, Aran E., Managh, Amy J., Stringer, Tameryn ORCID: https://orcid.org/0000-0002-4439-131X and Lord, Rianne M. ORCID: https://orcid.org/0000-0001-9981-129X (2024) Fluorinated N‑heterocyclic carbene silver(I) complexes with high cancer cell selectivity. Organometallics. ISSN 0276-7333

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Abstract

This work presents the synthesis of five new functionalized (benz)imidazolium N-heterocyclic (NHC) ligands (L) and four new (benz)imidazole silver(I) NHC (Ag(I)-NHC) complexes of mononuclear [Ag(L) 2 ](PF 6 ) or binuclear [Ag 2 (L) 2 ](PF 6 ) 2 type. The complexes have been fully characterized, including single crystal X-ray diffraction of three new structures. The complexes and their corresponding free NHC ligands have been screened against breast cancer and noncancerous cell lines, showing the mononuclear benzimidazole complex has the highest activity, while the binuclear benzimidazole complex has the highest cancer cell selectivity. The silver uptake was measured by ICP-MS and highlights a strong link between cytotoxicity and cellular uptake. DNA interaction studies, molecular docking, and evaluation of reactive oxygen species (ROS) have been conducted for the most promising complexes to identify modes of action. Overall, the binuclear benzimidazole complex is the most selective and promising candidate against the MDA-MD-231 (breast cancer) cell line and has potential to be developed for treatment of late-stage breast cancers.

Item Type: Article
Uncontrolled Keywords: sdg 3 - good health and well-being ,/dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being
Faculty \ School: Faculty of Science > School of Chemistry, Pharmacy and Pharmacology
Depositing User: LivePure Connector
Date Deposited: 03 Oct 2024 11:30
Last Modified: 07 Oct 2024 00:00
URI: https://ueaeprints.uea.ac.uk/id/eprint/96867
DOI: 10.1021/acs.organomet.4c00292

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