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Marine Drugs  2012 

Leucettamols, Bifunctionalized Marine Sphingoids, Act as Modulators of TRPA1 and TRPM8 Channels

DOI: 10.3390/md10112435

Keywords: leucettamols, TRP receptors, pain modulation

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Abstract:

Leucettamols, bifunctionalized sphingoid-like compounds obtained from a marine sponge Leucetta sp., act as non-electrophilic activators of the TRPA1 channel and potent inhibitors of the icilin-mediated activation of the TRPM8 channel, while they are inactive on CB 1, CB 2 and TRPV1 receptors. Leucettamols represent the first compounds of marine origin to target TRPA1 and the first class of natural products to inhibit TRPM8 channels. The preparation of a small series of semi-synthetic derivatives revealed interesting details on the structure-activity relationships within this new chemotype of simple acyclic TRP modulators.

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