Department of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, VIC 3010, Australia.
Griffith Institute for Drug Discovery, School of Environment and Science, Griffith University, Brisbane, QLD 4111, Australia.
Molecules. 2021 Sep 27;26(19):5846. doi: 10.3390/molecules26195846.
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 ( = 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 ()-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 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.
广泛的寄生虫线虫对大多数类别的驱虫药物的耐药性要求发现和开发具有独特作用机制的新型化合物，以补充战略或综合寄生虫控制计划。来自自然界的产品——假设具有多样化的“化学空间”——具有作为驱虫化合物来源的巨大潜力。在本研究中，我们在体外抗寄生虫活性的高通量生物测定中筛选了从澳大利亚水域采集的海洋无脊椎动物提取物（= 7616 个），以筛选对抗巴伯氏杆状线虫（）的活性，巴伯氏杆状线虫是一种具有经济重要性的家畜寄生虫线虫。在这个高通量筛选（HTS）中，我们确定了 58 个活性提取物，这些提取物将幼虫的运动性降低了≥70%（在 90 小时），总“命中率”约为 0.8%。在这 58 个提取物中，有 16 个提取物还将幼虫的发育抑制了≥80%（在 168 小时），并且/或者诱导了“非野生型”（异常）幼虫表型相对于未暴露于提取物（阴性对照）的“野生型”（正常）幼虫。最活跃的提取物（58 个中的 54 个）来自海绵，3 个来自脊索动物（被囊动物），1 个来自珊瑚；这些提取物代表了 23 个科的 37 个不同物种/分类群。利用 H NMR 指纹分析对样本进行分析，以消除重复出现的活性，并为进一步的化学研究确定一组 29 个海绵样本。总的来说，这些结果表明，来自澳大利亚水域的一系列海绵物种代表了具有杀线虫或杀线虫特性的天然化合物的丰富来源。我们现在的计划是专注于对本文中优先考虑的样本集进行深入的化学研究。
