Abstract
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 1H 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.
Highlights
Nematodes of the order Strongylida cause some of the most significant parasitic diseases of livestock worldwide, affecting hundreds of millions of food animals, with economic losses estimated at billions of dollars per annum globally [1]
Given the heavy reliance on anthelmintics in many parasite control programs, there is a need for the continued discovery and development of novel nematocides
Investigation of the active fractions from the two Haliclona collections led to the identification of halaminol A and a mixture of amino alcohol lipids as active components [14]. These findings show that marine sponges are a source of anthelmintic components/molecules
Summary
Nematodes (roundworms) of the order Strongylida (strongylids) cause some of the most significant parasitic diseases of livestock worldwide, affecting hundreds of millions of food animals (including sheep, goats, cattle and pigs), with economic losses estimated at billions of dollars per annum globally [1]. All of these properties or features would appear to enable the drug development process, which is why some of our recent anthelmintic discovery work has assessed products from nature Enabling this focus are: (a) the accessibility of curated, drug-like extract-, fractionand/or compound collections from natural sources; (b) the chemical diversity of natural products within these collections; (c) the availability of a phenotypic, whole-worm bioassays to screen these collections; and (d) the utility of advanced chromatographic, spectrometric and spectroscopic techniques for bioassay-guided fractionation and structural investigations (reviewed in [12]). This context has provided a sound basis for the identification and subsequent characterisation of anthelmintic molecules from natural sources. NMR Fingerprints of Extracts While the screening clearly identified that extracts from multiple sponge spe
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