title: Natural-Product-Derived Transient Receptor Potential Melastatin 8 (TRPM8) Channel Modulators.
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.
authors.affiliation: Department of Chemistry, University of Calgary , 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Christina M
authors.initials: CM
authors.lastname: LeGay
authors.affiliation: Department of Chemistry, University of Calgary , 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Evgueni
authors.initials: E
authors.lastname: Gorobets
authors.affiliation: Department of Physiology & Pharmacology, University of Calgary , 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Mircea
authors.initials: M
authors.lastname: Iftinca
authors.affiliation: Department of Physiology & Pharmacology, Schulich Medicine & Dentistry, University of Western Ontario , 1151 Richmond Street, London, Ontario, Canada N6A 3K7.
authors.forename: Rithwik
authors.initials: R
authors.lastname: Ramachandran
authors.affiliation: Department of Physiology & Pharmacology, University of Calgary , 3330 Hospital Drive NW, Calgary, Alberta, Canada T2N 4N1.
authors.forename: Christophe
authors.initials: C
authors.lastname: Altier
authors.affiliation: Department of Chemistry, University of Calgary , 2500 University Drive NW, Calgary, Alberta, Canada T2N 1N4.
authors.forename: Darren J
authors.initials: DJ
authors.lastname: Derksen