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High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters

Widespread resistance in parasitic nematodes to most classes of anthelmintic drugs demands the discovery and development of novel compounds with distinct mechanisms of action to complement strategic or integrated parasite control programs. Products from nature—which assume a diverse ‘chemical space’...

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Autores principales: Taki, Aya C., Byrne, Joseph J., Jabbar, Abdul, Lum, Kah Yean, Hayes, Sasha, Addison, Russell S., Ramage, Kelsey S., Hofmann, Andreas, Ekins, Merrick G., Wang, Tao, Chang, Bill C. H., Davis, Rohan A., Gasser, Robin B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512444/
https://www.ncbi.nlm.nih.gov/pubmed/34641389
http://dx.doi.org/10.3390/molecules26195846
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author Taki, Aya C.
Byrne, Joseph J.
Jabbar, Abdul
Lum, Kah Yean
Hayes, Sasha
Addison, Russell S.
Ramage, Kelsey S.
Hofmann, Andreas
Ekins, Merrick G.
Wang, Tao
Chang, Bill C. H.
Davis, Rohan A.
Gasser, Robin B.
author_facet Taki, Aya C.
Byrne, Joseph J.
Jabbar, Abdul
Lum, Kah Yean
Hayes, Sasha
Addison, Russell S.
Ramage, Kelsey S.
Hofmann, Andreas
Ekins, Merrick G.
Wang, Tao
Chang, Bill C. H.
Davis, Rohan A.
Gasser, Robin B.
author_sort Taki, Aya C.
collection PubMed
description Widespread resistance in parasitic nematodes to most classes of anthelmintic drugs demands the discovery and development of novel compounds with distinct mechanisms of action to complement strategic or integrated parasite control programs. Products from nature—which assume a diverse ‘chemical space’—have significant potential as a source of anthelmintic compounds. In the present study, we screened a collection of extracts (n = 7616) derived from marine invertebrates sampled from Australian waters in a high throughput bioassay for in vitro anti-parasitic activity against the barber’s pole worm (Haemonchus contortus)—an economically important parasitic nematode of livestock animals. In this high throughput screen (HTS), we identified 58 active extracts that reduced larval motility by ≥70% (at 90 h), equating to an overall ‘hit rate’ of ~0.8%. Of these 58 extracts, 16 also inhibited larval development by ≥80% (at 168 h) and/or induced ‘non-wild-type’ (abnormal) larval phenotypes with reference to ‘wild-type’ (normal) larvae not exposed to extract (negative controls). Most active extracts (54 of 58) originated from sponges, three from chordates (tunicates) and one from a coral; these extracts represented 37 distinct species/taxa of 23 families. An analysis of samples by (1)H NMR fingerprinting was utilised to dereplicate hits and to prioritise a set of 29 sponge samples for future chemical investigation. Overall, these results indicate that a range of sponge species from Australian waters represents a rich source of natural compounds with nematocidal or nematostatic properties. Our plan now is to focus on in-depth chemical investigations of the sample set prioritised herein.
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spelling pubmed-85124442021-10-14 High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters Taki, Aya C. Byrne, Joseph J. Jabbar, Abdul Lum, Kah Yean Hayes, Sasha Addison, Russell S. Ramage, Kelsey S. Hofmann, Andreas Ekins, Merrick G. Wang, Tao Chang, Bill C. H. Davis, Rohan A. Gasser, Robin B. Molecules Article Widespread resistance in parasitic nematodes to most classes of anthelmintic drugs demands the discovery and development of novel compounds with distinct mechanisms of action to complement strategic or integrated parasite control programs. Products from nature—which assume a diverse ‘chemical space’—have significant potential as a source of anthelmintic compounds. In the present study, we screened a collection of extracts (n = 7616) derived from marine invertebrates sampled from Australian waters in a high throughput bioassay for in vitro anti-parasitic activity against the barber’s pole worm (Haemonchus contortus)—an economically important parasitic nematode of livestock animals. In this high throughput screen (HTS), we identified 58 active extracts that reduced larval motility by ≥70% (at 90 h), equating to an overall ‘hit rate’ of ~0.8%. Of these 58 extracts, 16 also inhibited larval development by ≥80% (at 168 h) and/or induced ‘non-wild-type’ (abnormal) larval phenotypes with reference to ‘wild-type’ (normal) larvae not exposed to extract (negative controls). Most active extracts (54 of 58) originated from sponges, three from chordates (tunicates) and one from a coral; these extracts represented 37 distinct species/taxa of 23 families. An analysis of samples by (1)H NMR fingerprinting was utilised to dereplicate hits and to prioritise a set of 29 sponge samples for future chemical investigation. Overall, these results indicate that a range of sponge species from Australian waters represents a rich source of natural compounds with nematocidal or nematostatic properties. Our plan now is to focus on in-depth chemical investigations of the sample set prioritised herein. MDPI 2021-09-27 /pmc/articles/PMC8512444/ /pubmed/34641389 http://dx.doi.org/10.3390/molecules26195846 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Taki, Aya C.
Byrne, Joseph J.
Jabbar, Abdul
Lum, Kah Yean
Hayes, Sasha
Addison, Russell S.
Ramage, Kelsey S.
Hofmann, Andreas
Ekins, Merrick G.
Wang, Tao
Chang, Bill C. H.
Davis, Rohan A.
Gasser, Robin B.
High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters
title High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters
title_full High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters
title_fullStr High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters
title_full_unstemmed High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters
title_short High Throughput Screening of the NatureBank ‘Marine Collection’ in a Haemonchus Bioassay Identifies Anthelmintic Activity in Extracts from a Range of Sponges from Australian Waters
title_sort high throughput screening of the naturebank ‘marine collection’ in a haemonchus bioassay identifies anthelmintic activity in extracts from a range of sponges from australian waters
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8512444/
https://www.ncbi.nlm.nih.gov/pubmed/34641389
http://dx.doi.org/10.3390/molecules26195846
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