RuIII–Morpholine-Derived Thiosemicarbazone-Based Metallodrugs: Lysosome-Targeted Anticancer Agents

Abstract

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^III complexes 1–3 of morpholine-derived thiosemicarbazone ligands have been prepared and characterized by spectroscopy and HRMS along with the structure of 2 through a single-crystal X-ray diffraction study. The solution stability of 1–3 was tested using conventional techniques such as UV–vis and HRMS. Further, the anticancer activity of 1–3 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 1–3 with DNA and HSA were evaluated by different conventional methods such as absorption, fluorescence, and circular dichroism studies. Along with favorable biomolecule interaction, 1–3 revealed potent selectivity toward cancer cells, which is a prerequisite for the generation of an anticancer drug. According to cell viability results, 1 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. 1–3 disrupt the lysosome membrane potential by generating an excessive amount of reactive oxygen species, which results in an apoptotic mode of cell death.