Neuromodulating Alkaloids from Millipede Defensive Secretions
Carla Menegatti1, Jared S Wood2, Paige Banks1
1Department of Chemistry, Virginia Tech, Blacksburg, Virginia 24061, United States.
Journal of Natural Products
|January 24, 2025
Summary
Millipedes secrete complex terpenoid alkaloids, like the newly discovered ischnocybines, which disorient predators. Ischnocybine A specifically binds to the sigma-1 neuroreceptor, offering insight into millipede defense mechanisms.
Area of Science:
- Natural Product Chemistry
- Chemical Ecology
- Neurobiology
Background:
- Millipedes produce diverse chemical defenses, including less-studied terpenoid alkaloids.
- Alkaloids are known to disorient predators, but their specific biochemical targets remain unknown.
Purpose of the Study:
- To investigate the defensive secretions of the millipede *Ischnocybe plicata*.
- To elucidate the structure and properties of novel terpenoid alkaloids from this species.
- To identify the biochemical target of these defensive compounds.
Main Methods:
- Isolation and structural elucidation of alkaloids using various analytical techniques.
- Assessment of the defensive activity of secretions against ants.
- Neuroreceptor binding assays to evaluate interactions with sigma-1 and sigma-2 receptors.
Main Results:
- Four new, highly oxidized terpenoid alkaloids, named ischnocybines, were identified.
- Ischnocybines were actively secreted and demonstrated ant-disorienting properties.
- Ischnocybine A exhibited potent and selective binding to the sigma-1 neuroreceptor.
Conclusions:
- The discovered ischnocybines are the most complex millipede alkaloids found to date.
- This study provides the first potential biochemical target (sigma-1 receptor) for millipede alkaloid defenses.
- Findings advance understanding of chemical ecology and the evolution of invertebrate defense mechanisms.
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