Selected α-pyrones from the plants Cryptocarya novoguineensis (Lauraceae) and Piper methysticum (Piperaceae) with activity against Haemonchus contortus in vitro
Autor: | Sasha Hayes, Bill C.H. Chang, Andreas Hofmann, Tao Wang, H. M. P. Dilrukshi Herath, Rohan A. Davis, Jose F. Garcia-Bustos, Abdul Jabbar, R. S. Addison, Sarah Preston, Anson V. Koehler, Robin B. Gasser, Topul Rali |
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Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
0301 basic medicine
Cryptocarya α-pyrones Piper methysticum 030231 tropical medicine Phytochemicals Article lcsh:Infectious and parasitic diseases 03 medical and health sciences chemistry.chemical_compound Inhibitory Concentration 50 0302 clinical medicine Parasitic Sensitivity Tests Haemonchus contortus parasitic diseases medicine Anthelmintic Animals Pharmacology (medical) lcsh:RC109-216 Yangonin Avermectin Chromatography High Pressure Liquid Pharmacology Desmethoxyyangonin Anthelmintics Natural products biology Traditional medicine Plant Extracts Piperaceae biology.organism_classification High-Throughput Screening Assays 030104 developmental biology Infectious Diseases chemistry Cryptocarya novoguineensis Pyrones Larva Parasitology Haemonchus human activities medicine.drug |
Zdroj: | International Journal for Parasitology: Drugs and Drug Resistance, Vol 9, Iss, Pp 72-79 (2019) International Journal for Parasitology: Drugs and Drug Resistance |
ISSN: | 2211-3207 |
Popis: | 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. Graphical abstract Image 1 Highlights • 7500 plant extracts were screened against Haemonchus for anthelmintic activity. • Three of these extracts were potent inhibitors of larval motility and/or development. • Pure α-pyrones isolated from active fractions exhibited significant nematocidal activity. |
Databáze: | OpenAIRE |
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