Amoebicidal effect of Fluconazole and Verapamil together against trophozoites and cysts of Acanthamoeba castellanii

Abstract

Acanthamoeba species are an important pathogen that causes Acanthamoeba keratitis, which causes a visual loss, and encephalitis, which lead to the central nervous system infection and death. The options available to successfully treat Acanthamoeba infections have limited success. New therapeutic approaches must thus be developed, and especially combination medication therapy may be a successful and an effective strategy. The aim of this study was to assess the combination efficacy of verapamil and fluconazole against Acanthamoeba trophozoites and cysts. The effects of drugs on growth inhibition against Acanthamoeba were tested using amoebicidal assays. The viability of Acanthamoeba was assessed using Trypan blue and hemocytometer counts. The effect of three different concentrations of fluconazole, verapamil and fluconazole + verapamil combination on growth inhibition against Acanthamoeba trophozoites and cysts was significant compared to the control (p

Identification of Potent and Selective Inhibitors of Acanthamoeba: Structural Insights into Sterol 14α-Demethylase as a Key Drug Target

“…Voriconazole and fluconazole were chosen for further experiments as positive and negative controls, respectively. Both of these antifungals were reported to have some effectiveness in the treatment of human infections by Acanthamoeba (e.g., fluconazole, − voriconazole ,, ), suggesting that the chemical scaffolds with the 1 h IC 50 values lower than that of fluconazole (71 μM) can all be considered as potential leads for further drug design. Within the range (Figure ) were our synthesized imidazole-based VFV (29 μM), VNI (27 μM), and LFV (20 μM), the structures previously identified and further developed as inhibitors of protozoan or fungal CYP51 orthologs. − They were followed by the pyridine derivatives UDO (5.5 μM) and UDD (1.3 μM), the compounds from the Drugs for Neglected Diseases Initiative (DNDi), once considered as drug candidates for Chagas disease .…”