Quinizarin Gold(I) N-Heterocyclic Carbene Complexes with Synergistic Activity Against Anthracycline-Resistant Leukaemia Cells: Synthesis and Biological Activity Studies

被引：2

作者：

Steinbrueck, Axel ^{[1
]}

Reback, Matthew L. ^{[1
]}

Rumancev, Christoph ^{[2
]}

Siegmund, Daniel ^{[1
,3
]}

Garrevoet, Jan ^{[4
]}

Falkenberg, Gerald ^{[4
]}

Rosenhahn, Axel ^{[2
]}

Prokop, Aram ^{[5
,6
]}

Metzler-Nolte, Nils ^{[1
]}

机构：

[1] Ruhr Univ Bochum, Fac Chem & Biochem, Inorgan Chem Bioinorgan Chem 1, Univ Str 150, D-44801 Bochum, Germany

[2] Ruhr Univ Bochum, Fac Chem & Biochem, Analyt Chem Biointerfaces, Univ Str 150, D-44801 Bochum, Germany

[3] Fraunhofer UMSICHT, Div Energy, Osterfelder Str 3, D-46047 Oberhausen, Germany

[4] Deutsch Elektronen Synchrotron DESY, D-22607 Hamburg, Germany

[5] Helios Clin Schwerin, Dept Pediat Hematol Oncol, Wismarsche Str 393-397, D-19055 Schwerin, Germany

[6] Univ Appl Sci & Med Univ, MSH Med Sch, Dept Human Med, Kaiserkai 1, D-20457 Hamburg, Germany

来源：

CHEMISTRY-A EUROPEAN JOURNAL | 2025年 / 31卷 / 11期

关键词：

Cancer; Drug resistance; Gold; Medicinal inorganic chemistry; Metal-based drugs; N-heterocyclic carbene; X-ray fluorescence; METAL-COMPLEXES; INHIBITION;

D O I：

10.1002/chem.202404147

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

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 IC50 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 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.

引用

页数：8

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