Mohanty Monalisa, Das Sanchita, Pattanayak Pratikshya Das, Lima Sudhir, Kaminsky Werner, Dinda Rupam
Department of Chemistry, National Institute of Technology, Rourkela, Odisha 769008, India.
Department of Chemistry, University of Washington, Seattle, Washington 98195, United States.
ACS Appl Bio Mater. 2025 Feb 17;8(2):1210-1226. doi: 10.1021/acsabm.4c01536. Epub 2025 Jan 13.
The idea of coordinating biologically active ligand systems to metal centers to exploit their synergistic effects has gained momentum. Therefore, in this report, three Ru complexes - of morpholine-derived thiosemicarbazone ligands have been prepared and characterized by spectroscopy and HRMS along with the structure of through a single-crystal X-ray diffraction study. The solution stability of - was tested using conventional techniques such as UV-vis and HRMS. Further, the anticancer activity of - was tested in HT-29 and HeLa cancer cell lines. To gain insight into their mechanism of action, the cytotoxicity, hydrophobicity, and the interaction of - with DNA and HSA were evaluated by different conventional methods such as absorption, fluorescence, and circular dichroism studies. Along with favorable biomolecule interaction, - revealed potent selectivity toward cancer cells, which is a prerequisite for the generation of an anticancer drug. According to cell viability results, has the highest cytotoxicity among all in the group, against both cells, respectively. Additionally, the fluorescence-active ruthenium complexes selectively target lysosomes, which is evaluated by live-cell imaging. - disrupt the lysosome membrane potential by generating an excessive amount of reactive oxygen species, which results in an apoptotic mode of cell death.
将生物活性配体系统与金属中心配位以利用其协同效应的想法已获得发展势头。因此，在本报告中，制备了三种由吗啉衍生的硫代半卡巴腙配体的钌配合物，并通过光谱学、高分辨质谱以及通过单晶X射线衍射研究确定了其结构进行表征。使用紫外可见光谱和高分辨质谱等传统技术测试了其溶液稳定性。此外，在HT - 29和HeLa癌细胞系中测试了其抗癌活性。为深入了解其作用机制，通过吸收、荧光和圆二色性研究等不同传统方法评估了其细胞毒性、疏水性以及与DNA和人血清白蛋白的相互作用。除了具有良好的生物分子相互作用外，还显示出对癌细胞的有效选择性，这是产生抗癌药物的先决条件。根据细胞活力结果，在该组所有物质中对两种细胞分别具有最高的细胞毒性。此外，通过活细胞成像评估发现，具有荧光活性的钌配合物选择性靶向溶酶体。通过产生过量的活性氧破坏溶酶体膜电位，从而导致细胞凋亡的死亡模式。
