Journal article
Potent Inhibition of Thioredoxin Reductase by the Rh Derivatives of Anticancer M(arene/Cp*)(NHC)Cl2 Complexes
D Truong, MP Sullivan, KKH Tong, TR Steel, A Prause, JH Lovett, JW Andersen, SMF Jamieson, HH Harris, I Ott, CM Weekley, K Hummitzsch, T Söhnel, M Hanif, N Metzler-Nolte, DC Goldstone, CG Hartinger
Inorganic Chemistry | AMER CHEMICAL SOC | Published : 2020
Abstract
Metal complexes provide a versatile platform to develop novel anticancer pharmacophores, and they form stable compounds with N-heterocyclic carbene (NHC) ligands, some of which have been shown to inhibit the cancer-related selenoenzyme thioredoxin reductase (TrxR). To expand a library of isostructural NHC complexes, we report here the preparation of RhIII- and IrIII(Cp*)(NHC)Cl2 (Cp∗ = η5-pentamethylcyclopentadienyl) compounds and comparison of their properties to the RuII- and OsII(cym) analogues (cym = η6-p-cymene). Like the RuII- and OsII(cym) complexes, the RhIII- and IrIII(Cp*) derivatives exhibit cytotoxic activity with half maximal inhibitory concentration (IC50) values in the low mic..
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Awarded by U.S. Department of Energy
Funding Acknowledgements
We thank the Univ. of Auckland and the Cancer Research Trust New Zealand for financial support. N.M.-N. is grateful for a Julius-von-Haast Fellowship from the Royal Society of New Zealand. C.M.W. acknowledges the support of the NHMRC CJ Martin Overseas Biomedical Fellowship APP1090612. The authors are grateful to T. Groutso and T. Chen for collecting the single -crystal X-ray diffraction and ESIMS data, respectively. This research was undertaken in part using the XFM82 beamlines at the Australian Synchrotron, part of ANSTO. This research used resources of the Advanced Photon Source, a U.S. Department of Energy (DOE) Office of Science User Facility operated for the DOE Office of Science by Argonne National Laboratory under Contract No. DE-ACO2-06CH11357. Travel funding to perform experiments at the Advanced Photon Source was provided by the International Synchrotron Access Program managed by the Australian Synchrotron, part of ANSTO, funded by the Australian Government.