Cyclometalated iridium(III) complexes combined with fluconazole: antifungal activity against resistant .

() is a ubiquitous clinical fungal pathogen. In recent years, combination therapy, a potential treatment method to overcome resistance, has gained traction. In this study, we synthesized a series of cyclometalated iridium(III) complexes with the formula Ir(C-N)(tpphz) (C-N = 2-phenylpyridine (ppy, in ), 2-(2-thienyl)pyridine (thpy, in ), 2-(2,4-difluorophenyl) pyridine (dfppy, in ), tpphz = tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2''',3'''-j]phenazine) and polypyridyl ruthenium(II) complexes with the formula Ru(N-N)(tpphz) (N-N = 2,2'-bipyridine (bpy, in ), 1,10-phenanthroline (phen, in ), 4,7-diphenyl-1,10-phenanthroline (DIP, in )), and investigated their antifungal activities against drug-resistant and their combination with fluconazole (FLC). Of which, the combination of the lead iridium(III) complex and FLC showed strong antifungal activity against drug-resistant Mechanism studies have shown that they can inhibit the formation of hyphae and biofilm, damage mitochondrial function and accumulate intracellular ROS. Therefore, iridium(III) complexes combined with FLC can be used as a promising treatment to exert anti-drug-resistant activity, in order to improve the treatment efficiency of fungal infection.