Screening of a small, well-curated natural product-based library identifies two rotenoids with potent nematocidal activity against Haemonchus contortus

Herath, H. M. P. Dilrukshi; Preston, Sarah; Hofmann, Andreas; Davis, Rohan A.; Koehler, Anson V.; Chang, Bill C.H.; Jabbar, Abdul; Gasser, Robin B.

doi:10.1016/j.vetpar.2017.07.005

Cited by 19 publications

(14 citation statements)

References 54 publications

(64 reference statements)

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“…The isoflavonoids deguelin and rotenone (Fig. 4) were discovered from a screen of a small natural product library against exsheathed third-stage (xL3) larvae of H. contortus [56]. The two compounds are commonly isolated from plants of the family Leguminosae [57] and have been reported previously to display a range of activities, such as anti-inflammatory [58], apoptotic [59] and insecticidal [60].…”

Section: Chemical Classes Of Natural Compounds Described As Anthelminmentioning

confidence: 99%

An appraisal of natural products active against parasitic nematodes of animals

Garcia-Bustos

Sleebs

2019

Parasites Vectors

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Here, the scientific and patent literature on the activities of purified natural compounds has been reviewed, with the aim of assessing their suitability as anthelmintic drug discovery starting points. Only compounds described as active against parasitic nematodes of animals or against the model nematode Caenorhabditis elegans have been analysed. Scientific articles published since 2010 and patents granted from 2000, both inclusive, have been included in this analysis. The results show a scarcity of novel chemical structures, a limited follow-up of compounds disclosed before 2010 and a bias towards the screening of plant products, almost to the exclusion of other sources, when microbial extracts have, historically, provided most starting points for anti-infective drugs. All plant products published in this period were previously known, alerting to the high re-discovery rates of a limited number of chemical classes from this source. The most promising compounds described in the literature reviewed here, namely the linear nemadectin-derivatives, are novel and of bacterial origin. Patented but otherwise unpublished spiroketal structures also appear as interesting scaffolds for future development. The patent literature confirmed that it is possible to patent derivatives of previously known products, making them valid starting points for translational research.

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Section: Chemical Classes Of Natural Compounds Described As Anthelminmentioning

confidence: 99%

An appraisal of natural products active against parasitic nematodes of animals

Garcia-Bustos

Sleebs

2019

Parasites Vectors

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“…Over the last years, we have been working toward this goal, with an emphasis on the discovery of novel nematocidal or nematostatic compounds for medical chemistry optimisation and subsequent development (e.g., Preston et al, 2016, 2017a; Herath et al, 2017; Jiao et al, 2017). The Griffith Institute for Drug Discovery maintains multiple compound collections, including NatureBank which contains natural product extracts ( n = 10,000) and fractions ( n = 50,000) derived from plants, marine invertebrates and fungi as well as 30,000 archived biota samples linked to most of these samples (Camp et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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

Herath

Preston

Jabbar

et al. 2019

International Journal for Parasitology: Drugs and Drug Resistan

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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.

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“…Other Celastraceae samples that were prioritised for large-scale extraction and isolation studies will be investigated in the future. The pure compounds reported in this paper will be added to the Davis Open-Access Compound Library which is housed at Compounds Australia, Griffith University [19,22,23,24,25] and will be tested in various bioassays in the future. It is worth mentioning and well-known that the chemical profile of a plant can vary due to different geographical locations and collection seasons; however, even though this research utilised only Queensland Celastraceae plants, the UHPLC-MS method developed here should be applicable to the chemical profiling of any plant sample.…”

Section: Discussionmentioning

confidence: 99%

Using UHPLC-MS Profiling for the Discovery of New Dihydro-β-Agarofurans from Australian Celastraceae Plant Extracts

Wibowo

Forster²,

Guymer³

et al. 2019

Molecules

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An analytical method using UHPLC-MS was developed and applied to 16 crude CH2Cl2 extracts from Australian Celastraceae plants; the endemic plant materials were accessed from Griffith University’s NatureBank resource and included bark, fruit, leaf, root, twig and mixed samples, all of which were collected from Queensland, Australia. The generated UHPLC-MS data were analysed and dereplicated using the scientific databases Dictionary of Natural Products and SciFinder Scholar in order to potentially identify new dihydro-β-agarofurans from local Celastraceae plants. These investigations led to the large-scale extraction and isolation work on a prioritised fruit sample that belonged to the rainforest plant Denhamia celastroides. Chemical investigations resulted in the purification of four new natural products, denhaminols O–R (1–4), along with the related and known compound, denhaminol G (5). The structures of all the new compounds were determined via detailed analysis of NMR and MS data.

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Screening of a small, well-curated natural product-based library identifies two rotenoids with potent nematocidal activity against Haemonchus contortus

Cited by 19 publications

References 54 publications

An appraisal of natural products active against parasitic nematodes of animals

An appraisal of natural products active against parasitic nematodes of animals

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

Using UHPLC-MS Profiling for the Discovery of New Dihydro-β-Agarofurans from Australian Celastraceae Plant Extracts

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