Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia.
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia; Faculty of Science and Technology, Federation University, Ballarat, Victoria 3350, Australia.
Int J Parasitol Drugs Drug Resist. 2019 Apr;9:72-79. doi: 10.1016/j.ijpddr.2018.12.006. Epub 2019 Jan 4.
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 (IC 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 (IC of 200-300 μM) at inhibiting L4 development, it was the only compound that reduced L4 motility (IC 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.
由于驱虫剂耐药性的广泛发生和传播，需要开发针对家畜寄生虫线虫的新药。诺贝尔获奖发现和开发的抗寄生虫药物阿维菌素和青蒿素重新激发了人们对探索天然产物作为驱虫剂的兴趣。在本研究中，我们对 7500 种植物提取物进行了体外活性筛选，以对抗反刍动物的重要病原体旋毛虫，旋毛虫。两种植物Cryptocarya novoguineensis和Piper methysticum 的驱虫提取物通过高效液相色谱（HPLC）进行了分离。随后，从具有显著生物活性的馏分中纯化了化合物。从两种植物的馏分中纯化了四种α-吡喃酮，即戈尼辛（GNT）、二氢卡瓦宁（DHK）、去甲氧基洋丁香素（DMY）和洋丁香素（YGN），GNT 从 C. novoguineensis 中纯化，DHK、DMY 和 YGN（=卡瓦内酯）从 P. methysticum 中纯化。三种卡瓦内酯诱导处理过的蜕鞘第三期幼虫（xL3s）发生致死、内脏（Evi）表型，DMY 和 YGN 对 xL3s 发育为第四期幼虫（L4s）的抑制作用具有中等活力（IC 值分别为 31.7±0.23 μM 和 23.7±2.05 μM）。尽管 GNT 抑制 L4 发育的效力有限（IC 为 200-300 μM），但它是唯一能降低 L4 运动性的化合物（IC 为 6.25-12.50 μM）。从每种植物中纯化的化合物以不可逆的方式影响 H. contortus。这些发现表明，应进一步研究α-吡喃酮的构效关系，以评估其作为驱虫剂的潜力。
