Iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol analogues as hypoxia active, GSH-resistant cancer cytoselective and mitochondria-targeting cancer stem cell therapeutic agents.

Herein, we have introduced a series of iridium(III)-Cp*-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol complexes via a convenient synthetic methodology, which act as hypoxia active and glutathione-resistant anticancer metallotherapeutics. The [IrIII(Cp*)(L5)(Cl)](PF6) (IrL5) complex exhibited the best cytoselectivity, GSH resistance and hypoxia effectivity in HeLa and Caco-2 cells among the synthesized complexes. IrL5 also exhibited highly cytotoxic effects on the HCT-116 CSC cell line. This complex was localized in the mitochondria and subsequent mitochondrial dysfunction was observed via MMP alteration and ROS generation on colorectal cancer stem cells. Cell cycle analysis also established the potential of this complex in mediating G2/M phase cell cycle arrest.

Ru(ii), Ir(iii), Re(i) and Rh(iii) based complexes as next generation anticancer metallopharmaceuticals.

Several anticancer drugs such as cisplatin, and its analogues, epirubicin, and doxorubicin are well known for their anticancer activity but the therapeutic value of these drugs comes with certain side effects and they cannot distinguish between normal and cancer cells. Thus, a major challenge for researchers around the world is to develop an anticancer drug with the least toxicity and more target specificity. With the successful reporting of NAMI-A and KP1019, a new path has emerged in the anticancer field. Recently, several Ru(ii) complexes have been reported for their anticancer activity due to their enhanced cellular uptake and selectivity towards cancer cells. Apart from the Ru(ii) complexes, a large amount of research has been carried out with Ir(iii), Re(i), and Rh(iii) based complexes, which exhibited promising anticancer activity. The present review reports various Ru(ii), Ir(iii), Re(i), and Rh(iii) based complexes for their anticancer activity based on their cytotoxicity profiles, biological targets and mechanism of action.

GSH-resistant and highly cytoselective ruthenium(II)-p-cymene-(imidazo[4,5-f][1,10]phenanthrolin-2-yl)phenol complexes as potential anticancer agents.

To avoid the side effects of the current popular platinum-based anticancer drugs, researchers have made tireless attempts to design appropriate GSH-resistant Ru(ii)-arene complexes. In this regard, luminescent ruthenium(ii)-p-cymene-imidazophenanthroline complexes were developed as promising highly cytoselective cancer theraputic agents for HeLa and Caco-2 cells.