Sorbonne Université, CNRS, Institut Parisien de Chimie Moléculaire, IPCM, 75005, Paris, France.
Institute of Medicinal and Pharmaceutical Chemistry, Technische Universität Braunschweig, Beethovenstrasse 55, 38106, Braunschweig, Germany.
Chemistry. 2021 Nov 11;27(63):15773-15785. doi: 10.1002/chem.202102751. Epub 2021 Oct 5.
A library of eleven cationic gold(III) complexes of the general formula [(C C)Au(N N)] when C C is either biphenyl or 4,4'-ditertbutyldiphenyl and N N is a bipyridine, phenanthroline or dipyridylamine derivative have been synthesized and characterized. Contrasting effects on the viability of the triple negative breast cancer cells MDA-MB-231 was observed from a preliminary screening. The antiproliferative activity of the seven most active complexes were further assayed on a larger panel of human cancer cells as well as on non-cancerous cells for comparison. Two complexes stood out for being either highly active or highly selective. Eventually, reactivity studies with biologically meaningful amino acids, glutathione, higher order DNA structures and thioredoxin reductase (TrxR) revealed a markedly different behavior from that of the well-known coordinatively isomeric [(C N C)Au(NHC)] structure. This makes the [(C C)Au(N N)] complexes a new class of organogold compounds with an original mode of action.
已经合成并表征了十一组通式为[(CC)Au(NN)]的阳离子金(III)配合物的库，其中 CC 是联苯或 4,4'-二叔丁基二苯，NN 是联吡啶、菲咯啉或二吡啶基胺衍生物。初步筛选观察到它们对三阴性乳腺癌细胞 MDA-MB-231 的存活能力有不同的影响。对七种最活跃的配合物的抗增殖活性进行了更大的人类癌细胞和非癌细胞面板上的进一步测定，以进行比较。有两个配合物因其高活性或高选择性而脱颖而出。最终，与具有生物学意义的氨基酸、谷胱甘肽、高阶 DNA 结构和硫氧还蛋白还原酶 (TrxR) 的反应性研究表明，它们的行为与众所周知的配位异构 [(CNC)Au(NHC)] 结构明显不同。这使得 [(CC)Au(NN)] 配合物成为具有原始作用模式的新型有机金化合物。
