Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge <i>Agelas axifera</i>
A recent high-throughput screening of the NatureBank marine extract library (7616 samples) identified an extract from the Australian marine sponge <i>Agelas axifera</i> with in vitro activity against an economically important parasitic nematode, <i>Haemonchus contortus</i> (b...
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MDPI AG
2025-07-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/23/7/276 |
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| author | Kanchana Wijesekera Aya C. Taki Joseph J. Byrne Darren C. Holland Ian D. Jenkins Merrick G. Ekins Anthony R. Carroll Robin B. Gasser Rohan A. Davis |
| author_facet | Kanchana Wijesekera Aya C. Taki Joseph J. Byrne Darren C. Holland Ian D. Jenkins Merrick G. Ekins Anthony R. Carroll Robin B. Gasser Rohan A. Davis |
| author_sort | Kanchana Wijesekera |
| collection | DOAJ |
| description | A recent high-throughput screening of the NatureBank marine extract library (7616 samples) identified an extract from the Australian marine sponge <i>Agelas axifera</i> with in vitro activity against an economically important parasitic nematode, <i>Haemonchus contortus</i> (barber’s pole worm). The bioassay-guided fractionation of the CH<sub>2</sub>Cl<sub>2</sub>/MeOH extract from <i>A. axifera</i> led to the purification of a new diterpene alkaloid, agelasine Z (<b>1</b>), together with two known compounds agelasine B (<b>2</b>) and oxoagelasine B (<b>3</b>). Brominated compounds (–)-mukanadin C (<b>4</b>) and 4-bromopyrrole-2-carboxylic acid (<b>5</b>) were also isolated from neighbouring UV-active fractions. All compounds, together with agelasine D (<b>6</b>) from NatureBank’s pure compound library, were tested for in vitro anthelmintic activity against exsheathed third-stage (xL3s) and fourth-stage larvae (L4s) of <i>H. contortus</i> and young adult <i>Caenorhabditis elegans</i>. Compounds <b>1</b>, <b>2</b> and <b>6</b> induced an abnormal “skinny” phenotype, while compounds <b>2</b> and <b>6</b> also reduced the motility of <i>H. contortus</i> L4s by 50.5% and 51.8% at 100 µM, respectively. The minimal activity of agelasines against <i>C. elegans</i> young adults suggests a possible species-specific mechanism warranting further investigation. For the first time, the unexpected lability of agelasine H-8′ was explored using kinetic studies, revealing rapid deuterium exchange in MeOH-<i>d</i><sub>4</sub> at room temperature. |
| format | Article |
| id | doaj-art-90505ac26dad47bd9c8b6621c8d203ee |
| institution | Kabale University |
| issn | 1660-3397 |
| language | English |
| publishDate | 2025-07-01 |
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| series | Marine Drugs |
| spelling | doaj-art-90505ac26dad47bd9c8b6621c8d203ee2025-08-20T03:32:27ZengMDPI AGMarine Drugs1660-33972025-07-0123727610.3390/md23070276Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge <i>Agelas axifera</i>Kanchana Wijesekera0Aya C. Taki1Joseph J. Byrne2Darren C. Holland3Ian D. Jenkins4Merrick G. Ekins5Anthony R. Carroll6Robin B. Gasser7Rohan A. Davis8Institute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaDepartment of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, AustraliaDepartment of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, AustraliaSchool of Molecular Sciences, The University of Western Australia, Crawley, WA 6009, AustraliaInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaBiodiversity and Geosciences, Queensland Museum, South Brisbane BC, QLD 4101, AustraliaInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaDepartment of Veterinary Biosciences, Melbourne Veterinary School, Faculty of Science, The University of Melbourne, Parkville, VIC 3010, AustraliaInstitute for Biomedicine and Glycomics, Griffith University, Brisbane, QLD 4111, AustraliaA recent high-throughput screening of the NatureBank marine extract library (7616 samples) identified an extract from the Australian marine sponge <i>Agelas axifera</i> with in vitro activity against an economically important parasitic nematode, <i>Haemonchus contortus</i> (barber’s pole worm). The bioassay-guided fractionation of the CH<sub>2</sub>Cl<sub>2</sub>/MeOH extract from <i>A. axifera</i> led to the purification of a new diterpene alkaloid, agelasine Z (<b>1</b>), together with two known compounds agelasine B (<b>2</b>) and oxoagelasine B (<b>3</b>). Brominated compounds (–)-mukanadin C (<b>4</b>) and 4-bromopyrrole-2-carboxylic acid (<b>5</b>) were also isolated from neighbouring UV-active fractions. All compounds, together with agelasine D (<b>6</b>) from NatureBank’s pure compound library, were tested for in vitro anthelmintic activity against exsheathed third-stage (xL3s) and fourth-stage larvae (L4s) of <i>H. contortus</i> and young adult <i>Caenorhabditis elegans</i>. Compounds <b>1</b>, <b>2</b> and <b>6</b> induced an abnormal “skinny” phenotype, while compounds <b>2</b> and <b>6</b> also reduced the motility of <i>H. contortus</i> L4s by 50.5% and 51.8% at 100 µM, respectively. The minimal activity of agelasines against <i>C. elegans</i> young adults suggests a possible species-specific mechanism warranting further investigation. For the first time, the unexpected lability of agelasine H-8′ was explored using kinetic studies, revealing rapid deuterium exchange in MeOH-<i>d</i><sub>4</sub> at room temperature.https://www.mdpi.com/1660-3397/23/7/276<i>Agelas axifera</i>agelasineanthelmintic activity<i>Haemonchus contortus</i><i>Caenorhabditis elegans</i>deuterium exchange |
| spellingShingle | Kanchana Wijesekera Aya C. Taki Joseph J. Byrne Darren C. Holland Ian D. Jenkins Merrick G. Ekins Anthony R. Carroll Robin B. Gasser Rohan A. Davis Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge <i>Agelas axifera</i> Marine Drugs <i>Agelas axifera</i> agelasine anthelmintic activity <i>Haemonchus contortus</i> <i>Caenorhabditis elegans</i> deuterium exchange |
| title | Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge <i>Agelas axifera</i> |
| title_full | Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge <i>Agelas axifera</i> |
| title_fullStr | Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge <i>Agelas axifera</i> |
| title_full_unstemmed | Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge <i>Agelas axifera</i> |
| title_short | Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge <i>Agelas axifera</i> |
| title_sort | anthelmintic potential of agelasine alkaloids from the australian marine sponge i agelas axifera i |
| topic | <i>Agelas axifera</i> agelasine anthelmintic activity <i>Haemonchus contortus</i> <i>Caenorhabditis elegans</i> deuterium exchange |
| url | https://www.mdpi.com/1660-3397/23/7/276 |
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