Molecular Catalysis, Catalysis Research Center and Department of Chemistry Department Technische Universität München, Lichtenbergstrasse 4, D-85748, Garching bei München, Germany.
Institute for Bioengineering and Biosciences, Departamento de Engenharia e Ciências Nucleares, Instituto Superior Técnico, Universidade de Lisboa, Av. Rovisco Pais 1, 1049-001, Lisboa, Portugal.
Chem Asian J. 2020 Sep 1;15(17):2754-2762. doi: 10.1002/asia.202000620. Epub 2020 Jul 31.
A series of histidine derived Au(I) bis-NHC complexes bearing different ester, amide and carboxylic acid functionalities as well as wingtip substituents is synthesized and characterized. The stability in aqueous media, in vitro cytotoxicity in a set of cancer cell lines (MCF7, PC3 and A2780/A2780cisR) along with the cellular uptake are evaluated. Stability tests suggest hydrolysis of the ester within 8 h, which might lead to deactivation. Furthermore, the bis-NHC system shows a sufficient stability against cysteine and the thiol containing peptide GSH. The benzyl ester and amide show the highest activity comparable to the benchmark compound cisplatin, with the ester only displaying a slightly lower cytotoxicity than the amide. A cellular uptake study revealed that the benzyl ester and the amide could have different intracellular distribution profiles but both complexes induce perturbations of the cellular physiological processes. The simple modifiability and high stability of the complexes provides a promising system for upcoming post modifications to enable targeted cancer therapy.
一系列含有不同酯、酰胺和羧酸官能团以及翼端取代基的组氨酸衍生的 Au(I) 双-NHC 配合物被合成并进行了表征。评估了它们在水介质中的稳定性、在一组癌细胞系（MCF7、PC3 和 A2780/A2780cisR）中的体外细胞毒性以及细胞摄取能力。稳定性测试表明，酯在 8 小时内发生水解，这可能导致失活。此外，双-NHC 体系对半胱氨酸和含巯基的肽 GSH 具有足够的稳定性。苄酯和酰胺显示出与参比化合物顺铂相当的最高活性，而酯的细胞毒性略低于酰胺。细胞摄取研究表明，苄酯和酰胺可能具有不同的细胞内分布特征，但两种配合物都能诱导细胞生理过程的紊乱。该配合物具有简单的可修饰性和高稳定性，为即将进行的后续修饰提供了一种有前途的靶向癌症治疗系统。
