Gold(I) NHC-based homo- and heterobimetallic complexes: synthesis, characterization and evaluation as potential anticancer agents

被引:98
作者
Bertrand, Benoit [1 ,2 ]
Citta, Anna [3 ]
Franken, Inge L. [2 ]
Picquet, Michel [1 ]
Folda, Alessandra [3 ]
Scalcon, Valeria [4 ]
Rigobello, Maria Pia [3 ]
Le Gendre, Pierre [1 ]
Casini, Angela [2 ]
Bodio, Ewen [1 ]
机构
[1] Univ Bourgogne Franche Comte, CNRS, UMR 6302, Inst Chim Mol, F-21078 Dijon, France
[2] Univ Groningen, Res Inst Pharm, Dept Pharmacokinet Toxicol & Targeting, NL-9713 AV Groningen, Netherlands
[3] Univ Padua, Dept Biomed Sci, Padua, Italy
[4] CNR, Inst Neurosci, Padua, Italy
来源
JOURNAL OF BIOLOGICAL INORGANIC CHEMISTRY | 2015年 / 20卷 / 06期
关键词
N-heterocyclic carbene; Bimetallic complex; Gold complex; Anticancer drug; Thioredoxin reductase; HETEROCYCLIC CARBENE COMPLEXES; MITOCHONDRIAL THIOREDOXIN REDUCTASE; ARENE COMPLEXES; CYTOTOXIC PROPERTIES; VIBRATIONAL-SPECTRA; HALIDE COMPLEXES; INHIBITION; PURIFICATION; CHEMISTRY; CISPLATIN;
D O I
10.1007/s00775-015-1283-1
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
While N-heterocyclic carbenes (NHC) are ubiquitous ligands in catalysis for organic or industrial syntheses, their potential to form transition metal complexes for medicinal applications has still to be exploited. Within this frame, we synthesized new homo- and heterobimetallic complexes based on the Au(I)-NHC scaffold. The compounds were synthesized via a microwave-assisted method developed in our laboratories using Au(I)-NHC complexes carrying a pentafluorophenol ester moiety and another Au(I) phosphane complex or a bipyridine ligand bearing a pendant amine function. Thus, we developed two different methods to prepare homo- and heterobimetallic complexes (Au(I)/Au(I) or Au(I)/Cu(II), Au(I)/Ru(II), respectively). All the compounds were fully characterized by several spectroscopic techniques including far infrared, and were tested for their antiproliferative effects in a series of human cancer cells. They showed moderate anticancer properties. Their toxic effects were also studied ex vivo using the precision-cut tissue slices (PCTS) technique and initial results concerning their reactivity with the seleno-enzyme thioredoxin reductase were obtained.
引用
收藏
页码:1005 / 1020
页数:16
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