Screening The Pathogen Box for Identification of New Chemicals Agents With Anti Fasciola hepatica Activity [Experimental Therapeutics]

Fascioliasis is an infectious parasitic disease distributed globally and caused by the liver flukes Fasciola hepatica or F. gigantica. This neglected tropical disease affects both animals and humans and it represents a latent public health problem due to the significant economic losses related to animal husbandry. For decades, Triclabendazole has been the unique anti-Fasciola drug that can effectively treat this disease. However, triclabendazole resistance in Fascioliasis has been more recently reported around the world, and thus the discovery of novel drugs is an urgent need. The aim of this study was to investigate the fasciocidal properties of 400 compounds contained in the Pathogen Box. The first stage of the screening was carried out by measuring the fasciocidal activity on metacercariae at a concentration of 33 µM of each compound (standard dose). Subsequently the 50% inhibitory concentration (IC₅₀) values of the most active compounds (n=33) were assayed on metacercariae and resulted in 13 compounds with IC₅₀ ≤ 10 µM. The second stage queried these compounds at 33 µM on adult flukes where seven showed high mortality rates > 50%. Four hit compounds were selected based on predicted nontoxic properties and IC₅₀ values obtained on adult worms resulted < 10 µM thus representing the best fasciocidal compounds tested here. Cytotoxicity assay on four types of cell lines demonstrated that three compounds are nontoxic at its most active concentration. In conclusion, three hit compounds identified in this proof-of-concept study are potential candidates in the discovery of new fasciocidal drugs. Further studies are warranted.

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