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

Anand Chakroborty, Deiniol Pritchard, Marc E. Bouillon, Anna Cervi, Alan Cookson, Charlotte Wild, Caroline Fenn, Joseph Payne, Peter Holdsworth, Colin Capner, Jenna O’Neill, Gilda Padalino Orcid Logo, Josephine Forde-Thomas, Sandeep Gupta, Brendan G. Smith, Maggie Fisher, Martina Lahmann, Mark S. Baird, Karl F. Hoffmann

Veterinary Parasitology, Volume: 309, Start page: 109766

Swansea University Author: Gilda Padalino Orcid Logo

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DOI (Published version): 10.1016/j.vetpar.2022.109766

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 t...

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Published in: Veterinary Parasitology
ISSN: 0304-4017
Published: Elsevier BV 2022
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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</abstract><type>Journal Article</type><journal>Veterinary Parasitology</journal><volume>309</volume><journalNumber/><paginationStart>109766</paginationStart><paginationEnd/><publisher>Elsevier BV</publisher><placeOfPublication/><isbnPrint/><isbnElectronic/><issnPrint>0304-4017</issnPrint><issnElectronic/><keywords>Fasciola hepatica, Triclabendazole, Anthelmintic drug discovery, Abietic acid, Diterpene and dehydroabietic acid</keywords><publishedDay>30</publishedDay><publishedMonth>9</publishedMonth><publishedYear>2022</publishedYear><publishedDate>2022-09-30</publishedDate><doi>10.1016/j.vetpar.2022.109766</doi><url>http://dx.doi.org/10.1016/j.vetpar.2022.109766</url><notes/><college>COLLEGE NANME</college><department>Pharmacy</department><CollegeCode>COLLEGE CODE</CollegeCode><DepartmentCode>PHAR</DepartmentCode><institution>Swansea University</institution><apcterm/><funders>This work was supported and funded by UK Research and Innovation: Innovate UK grant number 102101.</funders><projectreference/><lastEdited>2023-10-10T10:40:11.1873110</lastEdited><Created>2023-09-05T16:07:30.3258456</Created><path><level id="1">Faculty of Medicine, Health and Life Sciences</level><level id="2">Swansea University Medical School - Pharmacy</level></path><authors><author><firstname>Anand</firstname><surname>Chakroborty</surname><order>1</order></author><author><firstname>Deiniol</firstname><surname>Pritchard</surname><order>2</order></author><author><firstname>Marc E.</firstname><surname>Bouillon</surname><order>3</order></author><author><firstname>Anna</firstname><surname>Cervi</surname><order>4</order></author><author><firstname>Alan</firstname><surname>Cookson</surname><order>5</order></author><author><firstname>Charlotte</firstname><surname>Wild</surname><order>6</order></author><author><firstname>Caroline</firstname><surname>Fenn</surname><order>7</order></author><author><firstname>Joseph</firstname><surname>Payne</surname><order>8</order></author><author><firstname>Peter</firstname><surname>Holdsworth</surname><order>9</order></author><author><firstname>Colin</firstname><surname>Capner</surname><order>10</order></author><author><firstname>Jenna</firstname><surname>O’Neill</surname><order>11</order></author><author><firstname>Gilda</firstname><surname>Padalino</surname><orcid>0000-0001-8580-1293</orcid><order>12</order></author><author><firstname>Josephine</firstname><surname>Forde-Thomas</surname><order>13</order></author><author><firstname>Sandeep</firstname><surname>Gupta</surname><order>14</order></author><author><firstname>Brendan G.</firstname><surname>Smith</surname><order>15</order></author><author><firstname>Maggie</firstname><surname>Fisher</surname><order>16</order></author><author><firstname>Martina</firstname><surname>Lahmann</surname><order>17</order></author><author><firstname>Mark S.</firstname><surname>Baird</surname><order>18</order></author><author><firstname>Karl F.</firstname><surname>Hoffmann</surname><order>19</order></author></authors><documents><document><filename>64429__28751__a859456533744364b5b53d9d8e973c8f.pdf</filename><originalFilename>64429.VOR.pdf</originalFilename><uploaded>2023-10-10T10:38:57.5691630</uploaded><type>Output</type><contentLength>3363696</contentLength><contentType>application/pdf</contentType><version>Version of Record</version><cronfaStatus>true</cronfaStatus><documentNotes>© 2022 The Author(s). 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spelling v2 64429 2023-09-05 Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica. 7e5526209f02734f57ba19b0d17604ec 0000-0001-8580-1293 Gilda Padalino Gilda Padalino true false 2023-09-05 PHAR 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 Journal Article Veterinary Parasitology 309 109766 Elsevier BV 0304-4017 Fasciola hepatica, Triclabendazole, Anthelmintic drug discovery, Abietic acid, Diterpene and dehydroabietic acid 30 9 2022 2022-09-30 10.1016/j.vetpar.2022.109766 http://dx.doi.org/10.1016/j.vetpar.2022.109766 COLLEGE NANME Pharmacy COLLEGE CODE PHAR Swansea University This work was supported and funded by UK Research and Innovation: Innovate UK grant number 102101. 2023-10-10T10:40:11.1873110 2023-09-05T16:07:30.3258456 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Pharmacy Anand Chakroborty 1 Deiniol Pritchard 2 Marc E. Bouillon 3 Anna Cervi 4 Alan Cookson 5 Charlotte Wild 6 Caroline Fenn 7 Joseph Payne 8 Peter Holdsworth 9 Colin Capner 10 Jenna O’Neill 11 Gilda Padalino 0000-0001-8580-1293 12 Josephine Forde-Thomas 13 Sandeep Gupta 14 Brendan G. Smith 15 Maggie Fisher 16 Martina Lahmann 17 Mark S. Baird 18 Karl F. Hoffmann 19 64429__28751__a859456533744364b5b53d9d8e973c8f.pdf 64429.VOR.pdf 2023-10-10T10:38:57.5691630 Output 3363696 application/pdf Version of Record true © 2022 The Author(s). Published by Elsevier B.V. Distributed under the terms of a Creative Commons Attribution 4.0 License (CC BY 4.0). true eng https://creativecommons.org/licenses/by/4.0/
title Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.
spellingShingle Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.
Gilda Padalino
title_short Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.
title_full Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.
title_fullStr Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.
title_full_unstemmed Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.
title_sort Flukicidal effects of abietane diterpenoid derived analogues against the food borne pathogen Fasciola hepatica.
author_id_str_mv 7e5526209f02734f57ba19b0d17604ec
author_id_fullname_str_mv 7e5526209f02734f57ba19b0d17604ec_***_Gilda Padalino
author Gilda Padalino
author2 Anand Chakroborty
Deiniol Pritchard
Marc E. Bouillon
Anna Cervi
Alan Cookson
Charlotte Wild
Caroline Fenn
Joseph Payne
Peter Holdsworth
Colin Capner
Jenna O’Neill
Gilda Padalino
Josephine Forde-Thomas
Sandeep Gupta
Brendan G. Smith
Maggie Fisher
Martina Lahmann
Mark S. Baird
Karl F. Hoffmann
format Journal article
container_title Veterinary Parasitology
container_volume 309
container_start_page 109766
publishDate 2022
institution Swansea University
issn 0304-4017
doi_str_mv 10.1016/j.vetpar.2022.109766
publisher Elsevier BV
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Pharmacy{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Pharmacy
url http://dx.doi.org/10.1016/j.vetpar.2022.109766
document_store_str 1
active_str 0
description 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
published_date 2022-09-30T10:40:13Z
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