Iridium(<scp>iii</scp>)–Cp*-(imidazo[4,5-<i>f</i>][1,10]phenanthrolin-2-yl)phenol analogues as hypoxia active, GSH-resistant cancer cytoselective and mitochondria-targeting cancer stem cell therapeutic agents

Abstract

Herein, we have introduced a series of iridium(III)-Cp*-(imidazo[4,5-<i>f</i>][1,10]phenanthrolin-2-yl)phenol complexes <i>via</i> a convenient synthetic methodology, which act as hypoxia active and glutathione-resistant anticancer metallotherapeutics. The [Ir^III(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 <i>via</i> 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.