In this work, we demonstrate bioorthogonal control of the phosphorescence and singlet oxygen photosensitisation properties of new iridium(iii) tetrazine complexes by different reaction partners; the s Show more
In this work, we demonstrate bioorthogonal control of the phosphorescence and singlet oxygen photosensitisation properties of new iridium(iii) tetrazine complexes by different reaction partners; the system was exploited for organelle-specific staining and modulated photocytotoxic activity applications. Show less
Current anticancer drug discovery efforts focus on the identification of first-in-class compounds with a mode-of-action distinct from conventional DNA-targeting agents for chemotherapy. An emerging tr Show more
Current anticancer drug discovery efforts focus on the identification of first-in-class compounds with a mode-of-action distinct from conventional DNA-targeting agents for chemotherapy. An emerging trend is the identification of endoplasmic reticulum (ER) targeting compounds that induce ER stress in cancer cells, leading to cell death. However, a limited pool of such compounds has been identified to date, and there are limited studies done on such compounds to allow for the rational design of ER stress-inducing agents. In our present study, we present a series of highly cytotoxic, ER stress-inducing Ru(II)-arene Schiff-Base (RAS) complexes, bearing iminoquinoline chelate ligands. We demonstrate that by structural modification to the iminoquinoline ligand, we could tune its π-acidity and influence reactive oxygen species (ROS) induction, switching between a ROS-mediated ER stress pathway activation and one that is not mediated by ROS induction. Our current study adds to the available ER stress inducers and shows how structural tuning could be used as a means to modulate the mode-of-action of such compounds. Show less
Two novel series of (salen)ruthenium(iii) complexes bearing guanidine and amidine axial ligands were synthesized, characterized, and evaluated for anticancer activity. In vitro cytotoxicity tes Show more
Two novel series of (salen)ruthenium(iii) complexes bearing guanidine and amidine axial ligands were synthesized, characterized, and evaluated for anticancer activity. In vitro cytotoxicity tests demonstrate that these complexes are cytotoxic against various cancer cell lines and the leading complexes have remarkable cancer-cell selectivity. A detailed study of the guanidine complex 7 and the amidine complex 13 reveals two distinguished modes of action. Complex 7 weakly binds to DNA and induces DNA damage, cell cycle arrest, and typical apoptosis pathways in MCF-7 cells. In contrast, complex 13 induces paraptosis-like cell death hallmarked by massive vacuole formation, mitochondrial swelling, and ER stress, resulting in significant cytotoxicity against human breast cancer cells. Our results provide an extraordinary example of tuning the mechanism of action of (salen)ruthenium(iii) anticancer complexes by modifying the structure of the axial ligands. Show less