Cysticidal Diamidines

About

Introduction: Acanthamoeba is a genus of amoebae that are among the most prevalent protozoa found in the environment. Several species of Acanthamoeba have been found to be responsible for the painful, sight-threatening disease of the cornea, Acanthamoeba keratitis. Severe conditions of this disease can require corneal transplants or even enucleation of the eye. Infection with Acanthamoeba keratitis is most commonly associated with contact lens use, particularly when lens wearers carry out improper lens disinfection or hygiene before handling contact lenses. Based on a population-based survey, in 2014, there were ~818,000 Acanthamoeba infections per year associated with contact lens wearers. However, the increasing number of people wearing contact lenses globally is resulting in a corresponding increase in Acanthamoeba infections as well. Some reports estimate a prevalence as high as 1.5 infections per 10,000 soft contact lens wearers annually depending on location. To make matters worse, multipurpose contact lens solutions are generally ineffective against Acanthamoeba. Current therapies are arduous. And because infectious generally involve a mixture of trophozoites and cysts, the therapies are poorly effective due to their inability to kill the protective cyst stage that can persist and cause a recurrent disease. Additionally, current therapeutic compounds have poor selectivity indices and are toxic with prolonged use in required cysticidal concentrations. Therefore, there is a strong need for new therapies against the Acanthamoeba species that exhibit broader, less toxic and more effective activity. Technology: Georgia State University researchers and their collaborators have discovered a potential Acanthamoeba treatment through a novel high-throughput, strain-specific, cysticidal assay. Fully mature cysts obtained by controlling encystation and excystation of each strain in vitro were used to test different compounds for cysticidal activity to find a novel class of diamidines. These diamidine-containing compounds, which are both trophocidal and cysticidal, showed acceptable cytotoxicity with selectivity index values greater than 10.