Anthelmintic Potential of Agelasine Alkaloids from the Australian Marine Sponge <i>Agelas axifera</i>

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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Bibliographic Details
Main Authors: 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
Format: Article
Language:English
Published: MDPI AG 2025-07-01
Series:Marine Drugs
Subjects:
<i>Agelas axifera</i>
agelasine
anthelmintic activity
<i>Haemonchus contortus</i>
<i>Caenorhabditis elegans</i>
deuterium exchange
Online Access:https://www.mdpi.com/1660-3397/23/7/276
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Summary: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.
ISSN:1660-3397

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