Antiproliferative Activity of Functionalized Histidine derived Au(I) bis-NHC Complexes for Bioconjugation.,Chemistry - An Asian Journal

当前位置： X-MOL 学术 › Chem. Asian J. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Antiproliferative Activity of Functionalized Histidine derived Au(I) bis-NHC Complexes for Bioconjugation.
Chemistry - An Asian Journal ( IF 3.5 ) Pub Date : 2020-06-27 , DOI: 10.1002/asia.202000620
Christian H G Jakob ₁ , Bruno Dominelli ₁ , Eva M Hahn ₁ , Tobias O Berghausen ₁ , Teresa Pinheiro ₂ , Fernanda Marques ₃ , Robert M Reich ₁ , João D G Correia ₃ , Fritz E Kühn ₁

Affiliation

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.

中文翻译：

用于生物共轭的功能化组氨酸衍生的 Au(I) 双 NHC 复合物的抗增殖活性。

合成并表征了一系列具有不同酯、酰胺和羧酸官能团以及翼尖取代基的组氨酸衍生的 Au(I)双-NHC 复合物。评估了水介质中的稳定性、一组癌细胞系（MCF7、PC3 和 A2780/A2780cisR）的体外细胞毒性以及细胞摄取。稳定性测试表明酯在 8 小时内水解，这可能导致失活。此外，双-NHC系统对半胱氨酸和含有硫醇的肽GSH表现出足够的稳定性。与基准化合物顺铂相比，苄基酯和酰胺表现出最高的活性，而酯仅表现出比酰胺略低的细胞毒性。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，但这两种复合物都会引起细胞生理过程的扰动。该复合物的简单可修饰性和高稳定性为即将进行的后修饰提供了一个有前途的系统，以实现靶向癌症治疗。

更新日期：2020-09-01

点击分享查看原文

点击收藏

阅读更多本刊最新论文