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Open AccessArticle

Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against Haemonchus contortus

1
Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, Australia
2
Faculty of Health and Life Sciences, Federation University, Ballarat, Victoria 3350, Australia
3
Griffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, Australia
4
Metabolic Research Unit, Metabolic Reprogramming Laboratory, School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria 3216, Australia
5
Queensland Museum, South Brisbane BC, QLD 4101, Australia
*
Authors to whom correspondence should be addressed.
Mar. Drugs 2019, 17(11), 598; https://doi.org/10.3390/md17110598
Received: 17 September 2019 / Revised: 16 October 2019 / Accepted: 20 October 2019 / Published: 23 October 2019
(This article belongs to the Collection Bioactive Compounds from Marine Invertebrates)
There is an urgent need to discover and develop new anthelmintics for the treatment of parasitic nematodes of veterinary importance to circumvent challenges linked to drug resistant parasites. Being one of the most diverse natural ecosystems, the marine environment represents a rich resource of novel chemical entities. This study investigated 2000 extracts from marine invertebrates, collected from Australian waters, for anthelmintic activity. Using a well-established in vitro bioassay, these extracts were screened for nematocidal activity against Haemonchus contortus — a socioeconomically important parasitic nematode of livestock animals. Extracts (designated Mu-1, Ha-1 and Ha-2) from two marine sponges (Monanchora unguiculata and Haliclona sp.) each significantly affected larvae of H. contortus. Individual extracts displayed a dose-dependent inhibition of both the motility of exsheathed third-stage larvae (xL3s) and the development of xL3s to fourth-stage larvae (L4s). Active fractions in each of the three extracts were identified using bioassay-guided fractionation. From the active fractions from Monanchora unguiculata, a known pentacyclic guanidine alkaloid, fromiamycalin (1), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC50) = 26.6 ± 0.74 µM) and L4 motility (IC50 = 39.4 ± 4.83 µM), although it had a relatively low potency at inhibiting of xL3 motility (IC50 ≥ 100 µM). Investigation of the active fractions from the two Haliclona collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (5). Anthelmintic profiling showed that 5 had limited potency at inhibiting larval development and motility. These data indicate that fromiamycalin, other related pentacyclic guanidine alkaloids and/or halaminols could have potential as anthelmintics following future medicinal chemistry efforts. View Full-Text
Keywords: marine; anthelmintic; Haemonchus contortus; alkaloid; fromiamycalin; halaminol A; Monanchora unguiculata; Haliclona sp marine; anthelmintic; Haemonchus contortus; alkaloid; fromiamycalin; halaminol A; Monanchora unguiculata; Haliclona sp
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Herath, H.M.P.D.; Preston, S.; Jabbar, A.; Garcia-Bustos, J.; Taki, A.C.; Addison, R.S.; Hayes, S.; Beattie, K.D.; McGee, S.L.; Martin, S.D.; Ekins, M.G.; Hooper, J.N.A.; Chang, B.C.H.; Hofmann, A.; Davis, R.A.; Gasser, R.B. Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against Haemonchus contortus. Mar. Drugs 2019, 17, 598.

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