Dual-functional cyclometalated iridium imine NHC complexes: highly potent anticancer and antimetastatic agents

Abstract

A new class of cyclometalated iridium(III) complexes with imine-N-heterocyclic carbenes (NHC) as ligands were synthesized and fully characterized. One crystal structure is reported. All the six complexes exhibited highly potent anticancer activity against A549 cells, HeLa cells, HepG2 cells, GL261 cells and A549R cells. In particular, they were up to 9 and 37 times more potent than clinically used anticancer drug cisplatin towards A549 and A549R cell lines, respectively. Remarkably, mechanism studies showed that the complexes pass into cancer cells through an energy-dependent pathway and cause apoptosis via reactive oxygen species (ROS) generation, mitochondrial membrane potential dysfunction, and lysosomal damage. In addition, complex Ir6 effectively impeded cell migration and colony formation.