Department of Chemistry and Biochemistry, University of California San Diego, 9500 Gilman Drive, La Jolla, CA, 92093, USA.
Department of Chemistry, Department of Materials Science & Engineering, Department of Biomedical Engineering and Department of Pharmacology, International Institute for Nanotechnology, Simpson Querrey Institute, Chemistry of Life Processes Institute and Lurie Cancer Center, Northwestern University, Evanston, Il, 60208, USA.
Chemistry. 2021 Feb 19;27(11):3772-3778. doi: 10.1002/chem.202004317. Epub 2021 Jan 19.
Cyclic (Alkyl)(Amino)Carbenes (CAACs) have become forceful ligands for gold due to their ability to form very strong ligand-metal bonds. Inspired by the success of Auranofin and other gold complexes as antitumor agents, we have studied the cytotoxicity of bis- and mono-CAAC-gold complexes on different cancer cell lines: HeLa (cervical cancer), A549 (lung cancer), HT1080 (fibrosarcoma) and Caov-3 (ovarian cancer). Further investigations aimed at elucidating their mechanism of action are described. This includes quantification of affinities for TrxR, evaluation of their bioavailability and determination of associated cell death process. Moreover, Transmission Electron Microscopy (TEM) was used to study morphological changes upon exposure. Noticeably, a significant reduction in non-specific binding to serum proteins was observed with CAAC complexes when compared to Auranofin. These results confirm the potential of CAAC-gold complexes in biological environments, which may result in more specific drug-target interactions and decreased side effects.
由于能够形成非常强的配体-金属键，环状（烷基）（氨基）卡宾（CAACs）已成为金的有力配体。受金诺芬和其他金配合物作为抗肿瘤剂成功的启发，我们研究了双和单 CAAC-金配合物对不同癌细胞系的细胞毒性：HeLa（宫颈癌）、A549（肺癌）、HT1080（纤维肉瘤）和 Caov-3（卵巢癌）。进一步的研究旨在阐明它们的作用机制。这包括定量测定它们与 TrxR 的亲和力，评估它们的生物利用度以及确定相关的细胞死亡过程。此外，还使用透射电子显微镜（TEM）研究了暴露后的形态变化。值得注意的是，与金诺芬相比，CAAC 配合物与血清蛋白的非特异性结合显著减少。这些结果证实了 CAAC-金配合物在生物环境中的潜力，这可能导致更特异的药物-靶标相互作用和减少副作用。
