Anticancer potential of polypyridyl-based Ir(III)-coumarin 6 conjugates under visible light and dark

Abstract

We developed and evaluated two novel coumarin 6 conjugated Ir(III) photocatalysts, [Ir(CO6)(Ph-tpy)Cl]Cl (Ir1) and [Ir(CO6)(An-tpy)Cl]Cl (Ir2) (CO6 = Coumarin 6, Ph-tpy = 4′-phenyl-2,2′:6′,2″-terpyridine, An-tpy = 4′-anthracenyl-2,2′:6′,2″-terpyridine), for application in cancer therapy. Upon green light irradiation (525 nm, 50.2 J cm−2), Ir1 and Ir2 effectively catalyzed NADH oxidation with turnover frequencies (TOFs) ranging from 840 to 1100 h−1 in phosphate-buffered saline. Additionally, these complexes generated reactive oxygen species (ROS), including 1O<inf>2</inf> and [rad]OH, through type I and type II mechanisms. Ir1 and Ir2 exhibited significant toxicity against human breast (MCF-7) and cervical (HeLa) cancer cells, with Ir2 demonstrating enhanced anticancer activity upon light activation. Notably, both complexes showed minimal dark toxicity toward non-cancerous human embryonic kidney (HEK-293) cells. The selectivity index (SI = Dark IC<inf>50</inf> in normal cells/Dark IC<inf>50</inf> in cancer cells) for Ir1 and Ir2 reached up to 22, highlighting their preferential activity in cancer cells. Mechanistic studies in MCF-7 cells with the most effective complex, Ir2, revealed that light exposure increased ROS production and induced mitochondrial depolarization and apoptosis via caspase 3/7 activation. © 2025 Elsevier B.V.