Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica Aberystwyth Univ, Inst Biol Environm & Rural Sci IBERS, Aberystwyth SY23 3DA, Dyfed, Wales..
Ridgeway Res Ltd, Pk Farm Bldg,Pk Lane, St Briavels GL15 6QX, Glos, England..
Ridgeway Res Ltd, Pk Farm Bldg,Pk Lane, St Briavels GL15 6QX, Glos, England..
Ridgeway Res Ltd, Pk Farm Bldg,Pk Lane, St Briavels GL15 6QX, Glos, England..
PAH Consultancy Pty Ltd, 3-27 Gaunson Crescent, Canberra, ACT 2903, Australia..
Ridgeway Res Ltd, Pk Farm Bldg,Pk Lane, St Briavels GL15 6QX, Glos, England..
Ridgeway Res Ltd, Pk Farm Bldg,Pk Lane, St Briavels GL15 6QX, Glos, England..
Aberystwyth Univ, Inst Biol Environm & Rural Sci IBERS, Aberystwyth SY23 3DA, Dyfed, Wales..
Aberystwyth Univ, Inst Biol Environm & Rural Sci IBERS, Aberystwyth SY23 3DA, Dyfed, Wales..
Bimeda UK, Bryn Cefni Ind Estate,Unit 2 A, Anglesey LL77 7XA, North Wales, Wales..
Bimeda UK, Bryn Cefni Ind Estate,Unit 2 A, Anglesey LL77 7XA, North Wales, Wales..
Ridgeway Res Ltd, Pk Farm Bldg,Pk Lane, St Briavels GL15 6QX, Glos, England..
Naturiol Bangor Ltd, MSParc, Gaerwen LL60 6AG, Anglesey, England..
Aberystwyth Univ, Inst Biol Environm & Rural Sci IBERS, Aberystwyth SY23 3DA, Dyfed, Wales..
Show others and affiliations
2022 (English) In: Veterinary parasitology, ISSN 0304-4017, E-ISSN 1873-2550, Vol. 309, p. 109766-, article id 109766Article in journal (Refereed) Published
Abstract [en]
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 mu M 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 mu M 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
Place, publisher, year, edition, pages Elsevier BV , 2022. Vol. 309, p. 109766-, article id 109766
Keywords [en]
Fasciola hepatica, Triclabendazole, Anthelmintic drug discovery, Abietic acid, Diterpene and dehydroabietic acid
National Category
Analytical Chemistry Other Medical Sciences not elsewhere specified Medicinal Chemistry
Identifiers URN: urn:nbn:se:kth:diva-317024 DOI: 10.1016/j.vetpar.2022.109766 ISI: 000842399400002 PubMedID: 35926239 Scopus ID: 2-s2.0-85135395632 OAI: oai:DiVA.org:kth-317024 DiVA, id: diva2:1693177
Note QC 20220906
2022-09-062022-09-062022-09-06 Bibliographically approved