Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against <em>Haemonchus contortus</em>
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 nove...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2019-10-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/17/11/598 |
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| author | H. M. P. Dilrukshi Herath Sarah Preston Abdul Jabbar Jose Garcia-Bustos Aya C. Taki Russell S. Addison Sasha Hayes Karren D. Beattie Sean L. McGee Sheree D. Martin Merrick G. Ekins John N. A. Hooper Bill C. H. Chang Andreas Hofmann Rohan A. Davis Robin B. Gasser |
| author_facet | H. M. P. Dilrukshi Herath Sarah Preston Abdul Jabbar Jose Garcia-Bustos Aya C. Taki Russell S. Addison Sasha Hayes Karren D. Beattie Sean L. McGee Sheree D. Martin Merrick G. Ekins John N. A. Hooper Bill C. H. Chang Andreas Hofmann Rohan A. Davis Robin B. Gasser |
| author_sort | H. M. P. Dilrukshi Herath |
| collection | DOAJ |
| description | 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 <i>Haemonchus contortus</i> — a socioeconomically important parasitic nematode of livestock animals. Extracts (designated <i>Mu</i>-1, <i>Ha</i>-1 and <i>Ha</i>-2) from two marine sponges (<i>Monanchora unguiculata</i> and <i>Haliclona</i> sp.) each significantly affected larvae of <i>H. contortus</i>. 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 <i>Monanchora unguiculata</i>, a known pentacyclic guanidine alkaloid, fromiamycalin (<b>1</b>), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC<sub>50</sub>) = 26.6 ± 0.74 µM) and L4 motility (IC<sub>50</sub> = 39.4 ± 4.83 µM), although it had a relatively low potency at inhibiting of xL3 motility (IC<sub>50</sub> ≥ 100 µM). Investigation of the active fractions from the two <i>Haliclona</i> collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (<b>5</b>). Anthelmintic profiling showed that <b>5</b> 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. |
| first_indexed | 2024-04-11T13:40:30Z |
| format | Article |
| id | doaj.art-3e28cf7ce12e43adb4bcb94d81ae4d7a |
| institution | Directory Open Access Journal |
| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-04-11T13:40:30Z |
| publishDate | 2019-10-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-3e28cf7ce12e43adb4bcb94d81ae4d7a2022-12-22T04:21:16ZengMDPI AGMarine Drugs1660-33972019-10-01171159810.3390/md17110598md17110598Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against <em>Haemonchus contortus</em>H. M. P. Dilrukshi Herath0Sarah Preston1Abdul Jabbar2Jose Garcia-Bustos3Aya C. Taki4Russell S. Addison5Sasha Hayes6Karren D. Beattie7Sean L. McGee8Sheree D. Martin9Merrick G. Ekins10John N. A. Hooper11Bill C. H. Chang12Andreas Hofmann13Rohan A. Davis14Robin B. Gasser15Faculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, AustraliaFaculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, AustraliaFaculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, AustraliaFaculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, AustraliaFaculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, AustraliaGriffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, AustraliaGriffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, AustraliaGriffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, AustraliaMetabolic Research Unit, Metabolic Reprogramming Laboratory, School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria 3216, AustraliaMetabolic Research Unit, Metabolic Reprogramming Laboratory, School of Medicine, Faculty of Health, Deakin University, Waurn Ponds, Victoria 3216, AustraliaQueensland Museum, South Brisbane BC, QLD 4101, AustraliaQueensland Museum, South Brisbane BC, QLD 4101, AustraliaFaculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, AustraliaFaculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, AustraliaGriffith Institute for Drug Discovery, Griffith University, Brisbane, QLD 4111, AustraliaFaculty of Veterinary and Agricultural Sciences, The University of Melbourne, Parkville, Victoria 3010, AustraliaThere 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 <i>Haemonchus contortus</i> — a socioeconomically important parasitic nematode of livestock animals. Extracts (designated <i>Mu</i>-1, <i>Ha</i>-1 and <i>Ha</i>-2) from two marine sponges (<i>Monanchora unguiculata</i> and <i>Haliclona</i> sp.) each significantly affected larvae of <i>H. contortus</i>. 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 <i>Monanchora unguiculata</i>, a known pentacyclic guanidine alkaloid, fromiamycalin (<b>1</b>), was purified. This alkaloid was shown to be a moderately potent inhibitor of L4 development (half-maximum inhibitory concentration (IC<sub>50</sub>) = 26.6 ± 0.74 µM) and L4 motility (IC<sub>50</sub> = 39.4 ± 4.83 µM), although it had a relatively low potency at inhibiting of xL3 motility (IC<sub>50</sub> ≥ 100 µM). Investigation of the active fractions from the two <i>Haliclona</i> collections led to identification of a mixture of amino alcohol lipids, and, subsequently, a known natural product halaminol A (<b>5</b>). Anthelmintic profiling showed that <b>5</b> 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.https://www.mdpi.com/1660-3397/17/11/598marineanthelmintic<i>haemonchus contortus</i>alkaloidfromiamycalinhalaminol a<i>monanchora unguiculata</i>haliclona sp |
| spellingShingle | H. M. P. Dilrukshi Herath Sarah Preston Abdul Jabbar Jose Garcia-Bustos Aya C. Taki Russell S. Addison Sasha Hayes Karren D. Beattie Sean L. McGee Sheree D. Martin Merrick G. Ekins John N. A. Hooper Bill C. H. Chang Andreas Hofmann Rohan A. Davis Robin B. Gasser Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against <em>Haemonchus contortus</em> Marine Drugs marine anthelmintic <i>haemonchus contortus</i> alkaloid fromiamycalin halaminol a <i>monanchora unguiculata</i> haliclona sp |
| title | Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against <em>Haemonchus contortus</em> |
| title_full | Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against <em>Haemonchus contortus</em> |
| title_fullStr | Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against <em>Haemonchus contortus</em> |
| title_full_unstemmed | Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against <em>Haemonchus contortus</em> |
| title_short | Identification of Fromiamycalin and Halaminol A from Australian Marine Sponge Extracts with Anthelmintic Activity against <em>Haemonchus contortus</em> |
| title_sort | identification of fromiamycalin and halaminol a from australian marine sponge extracts with anthelmintic activity against em haemonchus contortus em |
| topic | marine anthelmintic <i>haemonchus contortus</i> alkaloid fromiamycalin halaminol a <i>monanchora unguiculata</i> haliclona sp |
| url | https://www.mdpi.com/1660-3397/17/11/598 |
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