Acanthamoeba is a genus of free-living protozoa that can cause sight- and life-threatening diseases in man. Its control is still problematic due to the lack of effective and nontoxic acanthamoebicidal agents. Herein, we report the first finding of an in vitro killing effect of fusaric acid and dehydrofusaric acid, isolated from metabolites of the Fusarium fujikuroi species complex Tlau3, on Acanthamoeba trophozoites isolated from two clinical (AS, AR) and two soil (S3, S5) samples. AS, AR, and S3 were classified as members of the T4 genotype, whereas S5 belongs to T5. The fungal extract was found to exhibit acanthamoebicidal activity, and activity-guided fractionation led to the isolation and identification of active principles, fusaric acid and dehydrofusaric acid. Their effects were in concentration- and time-dependent manners. Fusaric acid and dehydrofusaric acid showed IC₅₀ values against AS trophozoites of 0.31 and 0.34 µM, respectively. Commercial fusaric acid displayed the same acanthamoebicidal activity as that of the isolated fusaric acid, and therefore, commercial fusaric acid was used throughout this study. IC₅₀ values of commercial fusaric acid against AR, S3, and S5 trophozoites were 0.33, 0.33, and 0.66 µM, respectively. Fusaric acid calcium salt has a history of usage as a hypotensive agent in humans with no observed toxicity. The present study suggests that fusaric acid may serve as a starting point for the development towards therapeutic and environmental acanthamoebicides with low toxicity to humans.
Georg Thieme Verlag KG Stuttgart · New York.