A structurally diverse library of 14 gold(I) cationic bis(NHC) and neutral mono(NHC) complexes (NHC: N‐heterocyclic carbene) was synthesized and characterized in this work. Four of them were new cationic gold(I) complexes containing functionalized NHCs, and their X‐ray crystal structures are presented herein. All of the complexes were investigated for their anticancer activities in four cancer cell lines, including a cisplatin‐resistant variant, and a noncancerous cell line. Seven of the cationic gold(I) complexes were found to display high and specific cytotoxic activities toward cancer cells. Two of them were even able to overcome cisplatin resistance. Two highly potent cationic complexes (11 and 15) were also submitted to the NCI‐60 cancer panel for further cytotoxicity evaluation. Complex 15 showed a surprisingly high potency toward leukemia among the nine examined cancer subtypes, particularly toward the CCRF‐CEM leukemia cell line with a concentration for 50 % inhibition of growth down to 79.4 nm. In addition, cationic complex 13, which demonstrated a remarkable cytotoxicity against hepatocellular carcinoma, was selected to obtain insight into the mechanistic aspects in HepG2 cells. Cellular uptake measurements were indicative of good bioavailability. By various biochemical assays, this complex was found to effectively inhibit thioredoxin reductase and its cytotoxicity toward HepG2 cells was found to be reactive oxygen species dependent.

中文翻译：

---

阳离子和中性N-杂环碳金（I）配合物：细胞毒性，NCI-60筛选，细胞吸收，抑制哺乳动物硫氧还蛋白还原酶和活性氧的形成

合成并表征了结构上多样的14个金（I）阳离子双（NHC）和中性单（NHC）配合物（NHC：N杂环卡宾）的文库。其中四个是含有功能化NHC的新型阳离子金（I）络合物，其X射线晶体结构在此显示。研究了所有复合物在四种癌细胞系中的抗癌活性，包括顺铂耐药变体和非癌细胞系。发现七个阳离子金（I）配合物显示出对癌细胞的高特异性细胞毒活性。他们中的两个甚至能够克服顺铂耐药性。两种高效阳离子络合物（11和15）也已提交给NCI-60癌症小组进行进一步的细胞毒性评估。复合物15在9种被检验的癌症亚型中表现出令人惊讶的高白血病效价，尤其是对CCRF-CEM白血病细胞株的效价，其浓度可抑制50％的生长直至79.4 n m。此外，选择了对肝细胞癌表现出显着细胞毒性的阳离子复合物13，以深入了解HepG2细胞的机制。细胞摄取测量表明良好的生物利用度。通过各种生化测定，发现该复合物有效抑制硫氧还蛋白还原酶，并且发现其对HepG2细胞的细胞毒性是反应性氧物种依赖性的。