Year-end Sale % OFF 
Abstract
AuIII 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 AuIII‐NHC complexes by direct oxidation with radioactive [124I]I2 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 AuIII‐to‐AuI reduction to achieve full anticancer activity, in vivo studies reveal that a fraction of the AuIII‐NHC prodrug is not immediately reduced after administration but able to reach the major organs before metabolic activation.
Highlights
The discovery that auranofin has potent anticancer effects,[1,2] together with the unceasing quest for metal-based drug alternatives to cisplatin and its analogues, has stimulated the development of Au complexes as novel chemotherapeutics against cancer.[3,4,5,6] The pioneering work of Che, Ott, Messori, and Casini, among others, demonstrated that AuI and AuIII complexes bearing N-heterocyclic carbene ligands (NHCs) display unique anticancer activity profiles in vitro[7,8,9] and reduce tumor size in treated mouse xenografts.[10,11,12,13,14]While the great majority of the studies have focused on AuI-NHCs, reports on AuIII analogues emerged more recently.[15,16,17,18] Under careful examination, these studies highlight that AuIII complexes frequently display antiproliferative effects comparable to their AuI counterparts.[19,20] The reason for such resemblance likely lies in the limited stability of AuIII-NHCs in biological environments and their rapid reduction to AuI metabolites
To understand the behavior of the AuIII-N-heterocyclic carbene (NHC) in biological systems, we evaluated their stability in solution by UV/Vis and 1H NMR spectroscopy
Serum reduction to 0.1 % resulted in an enhanced activity for all Au complexes, whereas the reducing hypoxic environment sensitized against auranofin but protected against Au-NHCs
Summary
The discovery that auranofin has potent anticancer effects,[1,2] together with the unceasing quest for metal-based drug alternatives to cisplatin and its analogues, has stimulated the development of Au complexes as novel chemotherapeutics against cancer.[3,4,5,6] The pioneering work of Che, Ott, Messori, and Casini, among others, demonstrated that AuI and AuIII complexes bearing N-heterocyclic carbene ligands (NHCs) display unique anticancer activity profiles in vitro[7,8,9] and reduce tumor size in treated mouse xenografts.[10,11,12,13,14]While the great majority of the studies have focused on AuI-NHCs, reports on AuIII analogues emerged more recently.[15,16,17,18] Under careful examination, these studies highlight that AuIII complexes frequently display antiproliferative effects comparable to their AuI counterparts.[19,20] The reason for such resemblance likely lies in the limited stability of AuIII-NHCs in biological environments and their rapid reduction to AuI metabolites. We describe a new strategy that exploits Au coordination chemistry for labeling AuIII-NHCs complexes with radioactive ligands and studying their organ accumulation in vivo.
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
