{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T02:43:29Z","timestamp":1789872209364,"version":"4.0.1"},"reference-count":46,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,3]],"date-time":"2023-07-03T00:00:00Z","timestamp":1688342400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006041","name":"UK Research and Innovation","doi-asserted-by":"publisher","award":["102101"],"award-info":[{"award-number":["102101"]}],"id":[{"id":"10.13039\/501100006041","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>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 \u03bcM and 13.02 \u03bcM, 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.<\/jats:p>","DOI":"10.3390\/pharmaceutics15071869","type":"journal-article","created":{"date-parts":[[2023,7,4]],"date-time":"2023-07-04T01:38:32Z","timestamp":1688434712000},"page":"1869","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Modified Hederagenin Derivatives Demonstrate Ex Vivo Anthelmintic Activity against Fasciola hepatica"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4987-2646","authenticated-orcid":false,"given":"Anand","family":"Chakroborty","sequence":"first","affiliation":[{"name":"The Department of Life Sciences (DLS), Aberystwyth University, Aberystwyth SY23 3DA, UK"},{"name":"Department of Cell Biology and Biochemistry, Texas Tech University Health Sciences Center, 3601 4th Street, Lubbock, TX 79430, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Deiniol R.","family":"Pritchard","sequence":"additional","affiliation":[{"name":"Naturiol Bangor Ltd., MSParc, Gaerwen, Anglesey LL60 6AG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc E.","family":"Bouillon","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Bangor University, Bangor LL57 2UW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Cervi","sequence":"additional","affiliation":[{"name":"Naturiol Bangor Ltd., MSParc, Gaerwen, Anglesey LL60 6AG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rolf","family":"Kraehenbuehl","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Bangor University, Bangor LL57 2UW, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"Wild","sequence":"additional","affiliation":[{"name":"Ridgeway Research Limited, Park Farm Buildings, Park Lane, St. Briavels, Gloucestershire GL15 6QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caroline","family":"Fenn","sequence":"additional","affiliation":[{"name":"Ridgeway Research Limited, Park Farm Buildings, Park Lane, St. Briavels, Gloucestershire GL15 6QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9173-5369","authenticated-orcid":false,"given":"Peter","family":"Holdsworth","sequence":"additional","affiliation":[{"name":"Ridgeway Research Limited, Park Farm Buildings, Park Lane, St. Briavels, Gloucestershire GL15 6QX, UK"},{"name":"PAH Consultancy Pty Ltd., 3\/27 Gaunson Crescent, Wanniassa, Canberra 2903, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7179-3755","authenticated-orcid":false,"given":"Colin","family":"Capner","sequence":"additional","affiliation":[{"name":"Ridgeway Research Limited, Park Farm Buildings, Park Lane, St. Briavels, Gloucestershire GL15 6QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gilda","family":"Padalino","sequence":"additional","affiliation":[{"name":"The Department of Life Sciences (DLS), Aberystwyth University, Aberystwyth SY23 3DA, UK"},{"name":"School of Pharmacy and Pharmaceutical Sciences, Cardiff University, Redwood Building, King Edward VII Avenue, Cardiff CF10 3NB, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7202-3565","authenticated-orcid":false,"given":"Josephine E.","family":"Forde-Thomas","sequence":"additional","affiliation":[{"name":"The Department of Life Sciences (DLS), Aberystwyth University, Aberystwyth SY23 3DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph","family":"Payne","sequence":"additional","affiliation":[{"name":"Ridgeway Research Limited, Park Farm Buildings, Park Lane, St. Briavels, Gloucestershire GL15 6QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brendan G.","family":"Smith","sequence":"additional","affiliation":[{"name":"Bimeda UK, Bryn Cefni Industrial Estate, Unit 2A, Llangefni LL77 7XA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maggie","family":"Fisher","sequence":"additional","affiliation":[{"name":"Ridgeway Research Limited, Park Farm Buildings, Park Lane, St. Briavels, Gloucestershire GL15 6QX, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8513-1952","authenticated-orcid":false,"given":"Martina","family":"Lahmann","sequence":"additional","affiliation":[{"name":"School of Natural Sciences, Bangor University, Bangor LL57 2UW, UK"},{"name":"KTH Royal Institute of Technology, Biomedical Engineering and Health Systems, H\u00e4lsov\u00e4gen 11, 141 52 Huddinge, Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5340-8745","authenticated-orcid":false,"given":"Mark S.","family":"Baird","sequence":"additional","affiliation":[{"name":"Naturiol Bangor Ltd., MSParc, Gaerwen, Anglesey LL60 6AG, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl F.","family":"Hoffmann","sequence":"additional","affiliation":[{"name":"The Department of Life Sciences (DLS), Aberystwyth University, Aberystwyth SY23 3DA, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,3]]},"reference":[{"key":"ref_1","unstructured":"Roberts, L.S., Janovy, J., and Schmidt, G.D. 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