Due to the widespread occurrence and spread of anthelmintic resistance, there is a need to develop new drugs against resistant parasitic nematodes of livestock animals. The Nobel Prize-winning discovery and development of the anti-parasitic drugs avermectin and artemisinin has renewed the interest in exploring natural products as anthelmintics. In the present study, we screened 7500 plant extracts for in vitro-activity against the barber's pole worm, Haemonchus contortus, a highly significant pathogen of ruminants. The anthelmintic extracts from two plants, Cryptocarya novoguineensis and Piper methysticum, were fractionated by high-performance liquid chromatography (HPLC). Subsequently, compounds were purified from fractions with significant biological activity. Four α-pyrones, namely goniothalamin (GNT), dihydrokavain (DHK), desmethoxyyangonin (DMY) and yangonin (YGN), were purified from fractions from the two plants, GNT from C. novoguineensis, and DHK, DMY and YGN (= kavalactones) from P. methysticum. The three kavalactones induced a lethal, eviscerated (Evi) phenotype in treated exsheathed third-stage larvae (xL3s), and DMY and YGN had moderate potencies (IC50 values of 31.7 ± 0.23 μM and 23.7 ± 2.05 μM, respectively) at inhibiting the development of xL3s to fourth-stage larvae (L4s). Although GNT had limited potency (IC50 of 200-300 μM) at inhibiting L4 development, it was the only compound that reduced L4 motility (IC50 of 6.25-12.50 μM). The compounds purified from each plant affected H. contortus in an irreversible manner. These findings suggest that structure-activity relationship studies of α-pyrones should be pursued to assess their potential as anthelmintics.

中文翻译：

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从植物隐叶藻（新种）和胡椒属（Piperaceae）中选出的α-吡喃酮具有体外抗捻转血矛线虫的活性。

由于驱虫抗药性的广泛发生和扩散，需要开发新的抗家畜抗药性线虫的药物。抗寄生虫药阿维菌素和青蒿素的诺贝尔奖获得者的发现和开发重新激发了人们对开发作为驱虫药的天然产品的兴趣。在本研究中，我们筛选了7500种植物提取物，以抗理发杆蠕虫Haemonchus contortus（一种非常重要的反刍动物病原体）的体外活性。通过高效液相色谱（HPLC）分离来自两种植物新隐隐孢子虫和胡椒的驱虫药提取物。随后，从具有明显生物学活性的馏分中纯化化合物。四个α-吡喃酮，分别为淋菌素（GNT），二氢卡哇因（DHK），从两株植物的级分中纯化去甲氧基仰光宁（DMY）和仰光宁（YGN），从新C. noguguensis的GNT，以及从P. methysticum的DHK，DMY和YGN（= kavalactones）纯化。这三个卡伐内酯在经处理的外来第三阶段幼虫（xL3s）中诱导了致死的，内脏的（Evi）表型，并且DMY和YGN在抑制发育方面具有中等效力（IC50值分别为31.7±0.23μM和23.7±2.05μM）。 xL3s到第四阶段的幼虫（L4s）。尽管GNT抑制L4发育的能力有限（IC50为200-300μM），但它是唯一降低L4运动性（IC50为6.25-12.50μM）的化合物。从每株植物中纯化得到的化合物都以不可逆的方式影响到捻转血吸虫。