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.

中文翻译：

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在血矛线虫生物测定中对 NatureBank“海洋收藏品”进行高通量筛选，鉴定了澳大利亚水域中一系列海绵提取物的驱虫活性


寄生线虫对大多数类别的驱虫药存在广泛的耐药性，需要发现和开发具有不同作用机制的新型化合物，以补充战略性或综合性寄生虫控制计划。自然界的产物——具有多样化的“化学空间”——作为驱虫化合物的来源具有巨大的潜力。在本研究中，我们通过高通量生物测定筛选了从澳大利亚水域采样的海洋无脊椎动物中提取的一系列提取物（ n = 7616），以检测其对捻转血矛线虫（ Haemonchus contortus ）（一种具有重要经济意义的寄生虫）的体外抗寄生虫活性。家畜线虫。在此高通量筛选 (HTS) 中，我们鉴定了 58 种活性提取物，可将幼虫运动能力降低 ≥70%（90 小时），相当于总体“命中率”约为 0.8%。在这 58 种提取物中，16 种还抑制幼虫发育 ≥80%（168 小时）和/或相对于未接触过的“野生型”（正常）幼虫诱导“非野生型”（异常）幼虫表型提取物（阴性对照）。大多数活性提取物（58 种中的 54 种）来自海绵，三种来自脊索动物（被囊动物），一种来自珊瑚；这些提取物代表了 23 个科的 37 个不同物种/类群。通过¹ H NMR 指纹分析对样品进行分析，以消除重复命中，并优先考虑一组 29 个海绵样品，以供未来的化学研究。总体而言，这些结果表明，澳大利亚水域的一系列海绵物种代表了具有杀线虫或抑制线虫特性的天然化合物的丰富来源。我们现在的计划是重点对本文优先考虑的样品集进行深入的化学研究。