Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.

Authors Organisations
  • Anand Chakroborty(Author)
    Institute of Parasitology, Biology Centre of the Academy of Sciences of the Czech Republic
  • Deiniol Pritchard(Author)
    Naturiol Bangor Ltd.
  • Marc E. Bouillon(Author)
    Prifysgol Bangor | Bangor University
  • Anna Cervi(Author)
    Naturiol Bangor Ltd.
  • Alan Cookson(Author)
  • Charlotte Wild(Author)
    Ridgeway Research Limited
  • Caroline Fenn(Author)
    Ridgeway Research Limited
  • Joseph Payne(Author)
    Ridgeway Research Limited
  • Peter Holdsworth(Author)
    PAH Consultancy Pty Ltd
  • Colin Capner(Author)
    Ridgeway Research Limited
  • Jenna O'Neill(Author)
    Ridgeway Research Limited
  • Gilda Padalino(Author)
  • Josephine Forde-Thomas(Author)
  • Sandeep Gupta(Author)
    Bryn Cefni Industrial Estate
  • Brendan G. Smith(Author)
    Bryn Cefni Industrial Estate
  • Maggie Fisher(Author)
    Ridgeway Research Limited
  • Martina Lahmann(Author)
    Prifysgol Bangor | Bangor University
    KTH Royal Institute of Technology
  • Mark S. Baird(Author)
    Naturiol Bangor Ltd.
  • Karl Hoffmann(Author)
Type Article
Original languageEnglish
Article number109766
Number of pages9
JournalVeterinary Parasitology
Volume309
Early online date01 Aug 2022
DOI
Publication statusPublished - 01 Sep 2022
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Abstract

Control of liver fluke infections remains a significant challenge in the livestock sector due to widespread distribution of drug resistant parasite populations. In particular, increasing prevalence and economic losses due to infection with Fasciola hepatica is a direct result of drug resistance to the gold standard flukicide, triclabendazole. Sustainable control of this significant zoonotic pathogen, therefore, urgently requires the identification of new anthelmintics. Plants represent a source of molecules with potential flukicidal effects and, amongst their secondary metabolites, the diterpenoid abietic acids can be isolated in large quantities. In this study, nineteen (19) chemically modified abietic acid analogues (MC_X) were first evaluated for their anthelmintic activities against F. hepatica newly excysted juveniles (NEJs, from the laboratory-derived Italian strain); from this, 6 analogues were secondly evaluated for their anthelmintic activities against adult wild strain flukes. One analogue, MC010, was progressed further against 8-week immature- and 12-week mature Italian strain flukes. Here, MC010 demonstrated moderate activity against both of these intra-mammalian fluke stages (with an adult fluke EC50 = 12.97 µM at 72 h post culture). Overt mammalian cell toxicity of MC010 was inferred from the Madin-Darby bovine kidney (MDBK) cell line (CC50 = 17.52 µM at 24 h post culture) and demonstrated that medicinal chemistry improvements are necessary before abietic acid analogues could be considered as potential anthelmintics against liver fluke pathogens.

Keywords

  • Abietic acid, Anthelmintic drug discovery, Diterpene and dehydroabietic acid, Fasciola hepatica, Triclabendazole

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