Alkaloids from Millipede Secretions New Millipede-Derived Compounds Show Promise for Neurological Drug Development

Newly discovered alkaloid compounds from millipede secretions show potential for targeting neuroreceptors linked to pain and neurological disorders. Found in Andrognathus corticarius, the molecules may open new avenues for drug development once they can be synthesized in larger quantities.

Millipedes get a bad rap — their many legs put people off and could classify them as “creepy crawly.” But these anthropods’ secretions could hold the key to new drug discovery for the treatment of neurological diseases and pain. Chemist Emily Mevers and her team recently discovered a new set of complex structures in millipede secretions that can modulate specific neuroreceptors in ant brains.

The newly discovered structures fall into a class of naturally occurring compounds called alkaloids. The Mevers team named them the andrognathanols and the andrognathines after the producing millipede, Andrognathus corticarius, found on Virginia Tech’s Blacksburg campus in Stadium Woods. These discoveries were recently published in the Journal of the American Chemical Society.

Mevers specializes in leveraging the chemistry of underexplored ecological niches, in this case the millipede, in the name of drug discovery.

After collecting millipedes from under leaf litter and fallen branches in Stadium Woods, Mevers and team members used a variety of analytical tools to identify the compounds contained in the millipedes’ defensive glands. They also learned that the millipedes release these compounds to ward off predators while also sharing their location with their kin.

Despite their pervasiveness, much about millipedes remains mysterious — including their specific habitats, numbers, diets, behaviors, and chemistry. Mevers, in collaboration with millipede expert Paul Marek in the entomology department, is working to fill in some of these gaps and see if what they uncover could be useful for future medications.

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Previously, Mevers and Marek examined a millipede native to the Pacific Northwest, Ishcnocybe plicata, and discovered that related alkaloids potently and selectively interact with a single neuroreceptor called Sigma-1. The interaction suggested that this family of compounds may have useful pharmacology potential for the treatment of pain and other neurological disorders.

The Mevers group discovered that the new alkaloids are actively secreted from the Hokie millipede when it is physically disturbed. The secretions cause disorientation in ants, a presumed natural predator. A subset of these compounds possesses similar interactions with the Sigma-1 neuroreceptor.

With the newfound complex compounds in hand, the next step is finding people to actually make them in larger quantities and evaluate their biomedical applications.

“These compounds are quite complex, so they're going to take some time to synthesize in the lab,” said Mevers.

Once larger quantities are available, Mevers will be able to better study their properties and potential in drug development.

Original Study: The Discovery of Complex Heterocycles from Millipede Secretions; Journal of the American Chemical Society; DOI 10.1021/jacs.5c08079

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