Quinizarin gold(I) N-heterocyclic carbene complexes with synergistic activity against anthracycline-aesistant leukaemia cells

Abstract

New, asymmetric quinizarin-Au(I)-NHC complexes were designed, isolated, and fully characterised including by single crystal X-ray crystallography. Cytotoxicity studies showed effective growth inhibition in HeLa cervical cancer cells with $IC_{50}$ values ranging from 2.4 $\mu$M to 5.3 $\mu$M. The successful cellular uptake was evidenced by X-ray fluorescence imaging on cryo-preserved whole HeLa cells and the sub-cellular localisation was monitored by live-cell fluorescence microscopy. Notably, complex $\bf {2 b}$ showed circumvention of acquired anthracycline resistance in K562 leukaemia cells as well as synergistic activity with doxorubicin against both wild-type and anthracycline-resistant Nalm-6 leukaemia cells. Interestingly, sub-cellular localisation towards mitochondria proved to be more important than the compounds’ overall cytotoxicity for potent antiproliferative activity and to achieve effective resistance circumvention