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Published on: December 31, 2013
Natural-Product-Derived Transient Receptor Potential Melastatin 8 (TRPM8) Channel Modulators
Christina M LeGay1, Evgueni Gorobets1, Mircea Iftinca2
1Department of Chemistry, University of Calgary , 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
Abstract:
A library of novel structural hybrids of menthol and cubebol was tested for each derivative's ability to interact with the transient receptor potential subfamily melastatin member 8 (TRPM8) channel. This structure-activity relationship study revealed three potent modulators of the TRPM8 ion channel: a novel agonist (4) with an EC50 value of 11 ± 1 μM, an antagonist (15) with an IC50 value of 2 ± 1 μM, and an allosteric modulator (21) that minimized channel desensitization toward menthol. Each of these novel exocyclic olefin analogues of menthol is readily accessible by synthesis and was tested using Ca(2+) assays and electrophysiology.
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