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Modified hederagenin derivatives demonstrate ex vivo anthelmintic activity against fasciola hepatica

Chakroborty, Anand, Pritchard, Deiniol R., Bouillon, Marc E., Cervi, Anna, Kraehenbuehl, Rolf, Wild, Charlotte, Fenn, Caroline, Holdsworth, Peter, Capner, Colin, Padalino, Gilda, Forde-Thomas, Josephine E., Payne, Joseph, Smith, Brendan G., Fisher, Maggie, Lahmann, Martina, Baird, Mark S. and Hoffmann, Karl F. 2023. Modified hederagenin derivatives demonstrate ex vivo anthelmintic activity against fasciola hepatica. Pharmaceutics 15 (7) , 1869. 10.3390/pharmaceutics15071869

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Infection with Fasciola hepatica (liver fluke) causes fasciolosis (or fascioliasis) and poses a considerable economic as well as welfare burden to both the agricultural and animal health sectors. Here, we explore the ex vivo anthelmintic potential of synthetic derivatives of hederagenin, isolated in bulk from Hedera helix. Thirty-six compounds were initially screened against F. hepatica newly excysted juveniles (NEJs) of the Italian strain. Eleven of these compounds were active against NEJs and were selected for further study, using adult F. hepatica derived from a local abattoir (provenance unknown). From these eleven compounds, six demonstrated activity and were further assessed against immature liver flukes of the Italian strain. Subsequently, the most active compounds (n = 5) were further evaluated in ex vivo dose response experiments against adult Italian strain liver flukes. Overall, MC042 was identified as the most active molecule and the EC50 obtained from immature and adult liver fluke assays (at 24 h post co-culture) are estimated as 1.07 μM and 13.02 μM, respectively. When compared to the in vitro cytotoxicity of MDBK bovine cell line, MC042 demonstrated the highest anthelmintic selectivity (44.37 for immature and 3.64 for adult flukes). These data indicate that modified hederagenins display properties suitable for further investigations as candidate flukicides.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Pharmacy
Additional Information: License information from Publisher: LICENSE 1: URL:, Type: open-access
Publisher: MDPI
Date of First Compliant Deposit: 9 August 2023
Date of Acceptance: 28 June 2023
Last Modified: 10 Aug 2023 01:37

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