Journal
ANGEWANDTE CHEMIE-INTERNATIONAL EDITION
Volume 59, Issue 39, Pages 17130-17136Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/anie.202008046
Keywords
anticancer; metallodrugs; N-heterocyclic carbenes; positron emission tomography; radiochemistry
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Funding
- EU Horizon 2020 Research and Innovation Programme under the Marie Sklodowska-Curie Actions [746976]
- Severo Ochoa Centres of Excellence Programme by the Spanish State Research Agency [CEX2018-000867-S]
- Spanish Ministry of Economy and Competitiveness [CTQ2017-87637-R]
- Beneficentia Stiftung
- University of Pisa [PRA_2017_25]
- Austrian Science Fund (FWF) [L212, L568]
- Spanish MultiMetDrugs network [RED2018-102471-T]
- Austrian Science Fund (FWF) [L568, L212] Funding Source: Austrian Science Fund (FWF)
- Marie Curie Actions (MSCA) [746976] Funding Source: Marie Curie Actions (MSCA)
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Au(III)complexes with N-heterocyclic carbene (NHC) ligands have shown remarkable potential as anticancer agents, yet their fate in vivo has not been thoroughly examined and understood. Reported herein is the synthesis of new Au-III-NHC complexes by direct oxidation with radioactive [I-124]I(2)as a valuable strategy to monitor the in vivo biodistribution of this class of compounds using positron emission tomography (PET). While in vitro analyses provide direct evidence for the importance of Au-III-to-Au(I)reduction to achieve full anticancer activity, in vivo studies reveal that a fraction of the Au-III-NHC prodrug is not immediately reduced after administration but able to reach the major organs before metabolic activation.
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