Key Laboratory of Xinjiang Phytomedicine Resources of Ministry of Education, School of Pharmacy, Shihezi University, Shihezi 832002, China; Key Laboratory for Green Processing of Chemical Engineering of Xinjiang Bingtuan, School of Chemistry and Chemical Engineering, Shihezi University, Shihezi 832003, China.
Shaanxi Key Laboratory of Natural Products & Chemical Biology, College of Chemistry & Pharmacy, Northwest Agriculture and Forestry University, Yangling, Shaanxi 712100, China.
Bioorg Chem. 2021 May;110:104749. doi: 10.1016/j.bioorg.2021.104749. Epub 2021 Feb 19.
Real-time monitoring of drug metabolism in vivo is of great significance to drug development and toxicology research. The purpose of this study is to establish a rapid and visual in vivo detection method for the detection of an intermediate metabolite of the gold (I) drug. Gold (I) drugs such as sodium aurothiomalate (AuTM) have anti-inflammatory effects in the treatment of rheumatoid arthritis. Gold(III) ions (Au) are the intermediate metabolite of gold medicine, and they are also the leading factor of side effects in the treatment of patients. However, the rapid reduction of Au to Au by thiol proteins in organisms limits the in-depth study of metabolism of gold drugs in vivo. Here we describe a luminescence Au probe (RA) based on ruthenium (II) complex for detecting Au in vitro and in vivo. RA with large Stokes shift, good water solubility and biocompatibility was successfully applied to detect Au in living cells and vivo by luminescence imaging, and to trap the fluctuation of Au level produced by gold (I) medicine. More importantly, the luminescent probe was used to the detection of the intermediate metabolites of gold (I) drugs for the first time. Overall, this work offers a new detection tool/method for a deeper study of gold (I) drugs metabolite.
实时监测体内药物代谢对于药物开发和毒理学研究具有重要意义。本研究旨在建立一种快速、可视化的体内检测方法，用于检测金（I）药物的一种中间代谢物。金（I）药物，如金硫丁二酸钠（AuTM），在治疗类风湿性关节炎方面具有抗炎作用。金（III）离子（Au）是金药物的中间代谢物，也是治疗患者时产生副作用的主要因素。然而，生物体内的巯基蛋白将 Au 快速还原为 Au，限制了对金药物体内代谢的深入研究。在这里，我们描述了一种基于钌（II）配合物的发光 Au 探针（RA），用于体外和体内检测 Au。RA 具有较大的斯托克斯位移、良好的水溶性和生物相容性，成功应用于通过发光成像检测活细胞和体内的 Au，并捕获金（I）药物产生的 Au 水平波动。更重要的是，首次将该发光探针用于检测金（I）药物的中间代谢物。总的来说，这项工作为更深入地研究金（I）药物代谢物提供了一种新的检测工具/方法。
