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Int J Parasitol Drugs Drug Resist. 2019 Apr;9:72-79. doi: 10.1016/j.ijpddr.2018.12.006. Epub 2019 Jan 4.

Selected α-pyrones from the plants Cryptocarya novoguineensis (Lauraceae) and Piper methysticum (Piperaceae) with activity against Haemonchus contortus in vitro.

Author information

1
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia.
2
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.
3
Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111, Australia.
4
School of Natural & Physical Sciences, The University of Papua New Guinea, PO Box 320, University 134, National Capital District, Papua New Guinea.
5
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia; Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111, Australia.
6
Griffith Institute for Drug Discovery, Griffith University, Don Young Road, Nathan, Queensland 4111, Australia. Electronic address: r.davis@griffith.edu.au.
7
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address: robinbg@unimelb.edu.au.

Abstract

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.

KEYWORDS:

Anthelmintic; Cryptocarya novoguineensis; Haemonchus contortus; Natural products; Piper methysticum; α-pyrones

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