Modified Hederagenin Derivatives Demonstrate Ex Vivo Anthelmintic Activity against Fasciola hepatica

Anand Chakroborty, Deiniol Pritchard, Marc E. Bouillon, Anna Cervi, Rolf Kraehenbuehl, Charlotte Wild, Caroline Fenn, Peter A. Holdsworth, Colin Capner, Gilda Padalino, Josephine Forde-Thomas, Joseph Payne, Brendan G. Smith, Maggie Fisher, Martina Lahmann, Mark S. Baird, Karl Hoffmann

Allbwn ymchwil: Cyfraniad at gyfnodolynErthygladolygiad gan gymheiriaid

62 Wedi eu Llwytho i Lawr (Pure)

Crynodeb

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.

Iaith wreiddiolSaesneg
Rhif yr erthygl1869
Nifer y tudalennau15
CyfnodolynPharmaceutics
Cyfrol15
Rhif cyhoeddi7
Dynodwyr Gwrthrych Digidol (DOIs)
StatwsCyhoeddwyd - 03 Gorff 2023

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