Photodynamic Inactivation of Candida albicans with Imidazoacridinones: Influence of Irradiance, Photosensitizer Uptake and Reactive Oxygen Species Generation.

摘要: The increasing applicability of antifungal treatments, the limited range available drug classes and emergence resistance in Candida spp. suggest need for new treatment options. To explore C. albicans photoinactivation, we examined nine structurally different imidazoacridinone derivatives as photosensitizing agents. most effective showed a >104-fold reduction viable cell numbers. fungicidal action three active compounds was compared at radiant powers(3.5 to 63 mW/cm2), this analysis indicated that 7 mW/cm2 efficient. intracellular accumulation these fungal cells correlated with activity all 9 derivatives. lack effect verapamil, an inhibitor targeting ABC efflux pumps, suggests imidazoacridinones are not substrates transporters. Thus, unlike azoles, major class antifungals used against Candida, transporter-mediated is unlikely. Electron paramagnetic resonance (EPR)-spin trapping data suggested light-induced might depend on production superoxide anion. highest generation rate anion observed 1330H, 1610H, 1611. Singlet oxygen also detected upon irradiation UV laser light, low moderate yield, depending type compound. present study act via mixed I/type II photodynamic mechanism. presented indicate direct correlation between structures studied imidazoacridinones, killing ability, ROS production. However, first time only necessary prerequisite lethal photosensitization albicans, but localization within particular cellular structures. Our findings IA efficient photosensitizers potential be local infection.