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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, 43 (20).
2662–2673.
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 |
|---|---|
| Additional Information: | Funding information: The University of East Anglia’s Faculty of Science Ph.D. studentship funds for O.S.K., and the UKRI Future Leader Fellow scheme [MR/T041315/1] for funding of B.J.H. and R.M.L. |
| 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: | 27 Nov 2024 10:44 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/96867 |
| DOI: | 10.1021/acs.organomet.4c00292 |
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