Effect of acyclic monoterpene alcohols and their derivatives on TRP channels

Ortar, Giorgio; Moriello, Aniello Schiano; Morera, Enrico; Nalli, Marianna; Marzo, Vincenzo Di; Petrocellis, Luciano De

doi:10.1016/j.bmcl.2014.10.012

Cited by 20 publications

(18 citation statements)

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“…The molecular conformations of (−)-carveol, 6- tert -butyl- m -cresol, carvacrol, and thymol were used for the model of TRPV3/TRPM8 agonists 23 , whereas conformations of capsaicin, N -geranyl cyclopropylcarboxamide (NGCC) 12 , and compound 2k 13 were used for the model of TRPV1 agonists.…”

Section: Resultsmentioning

confidence: 99%

“…Indeed, the shapes of their molecular fields are quite different from Templates A and B (e.g., see Figure 8D), confirming that geranylacetone and isobornyl acetate do not interact with the same molecular targets reflected by Templates A and B . On the other hand, the molecular structure of geranylacetone resembles such TRPV1 agonists as capsaicin and its analogs 12, 13 . Indeed, the pharmacophore model of TRPV1 agonists based on capsaicin, NGCC, and compound 2k 12, 13 ( Template C ) differs substantially from pharmacophore Templates A and B and contains two different hydrophobic regions.…”

Section: Resultsmentioning

confidence: 99%

“…On the other hand, the molecular structure of geranylacetone resembles such TRPV1 agonists as capsaicin and its analogs 12, 13 . Indeed, the pharmacophore model of TRPV1 agonists based on capsaicin, NGCC, and compound 2k 12, 13 ( Template C ) differs substantially from pharmacophore Templates A and B and contains two different hydrophobic regions. A large area of negative field (blue area in Figure 8E) surrounds the overlapping carbonyl groups and electron acceptor substituents in the aromatic rings.…”

Section: Resultsmentioning

confidence: 99%

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Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents

Schepetkin

Кушнаренко

Özek

et al. 2016

J. Agric. Food Chem.

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Essential oils were obtained by hydrodistillation of the umbels+seeds and stems of Ferula akitschkensis (FAEOu/s and FAEOstm, respectively) and analyzed by gas chromatography and gas chromatography–mass spectrometry. Fifty two compounds were identified in FAEOu/s. The primary components were sabinene, α-pinene, β-pinene, terpinen-4-ol, eremophilene, and 2-himachalen-7-ol, while the primary components of FAEOstm were myristicin and geranylacetone. FAEOu/s, β-pinene, sabinene, γ-terpinene, geranylacetone, isobornyl acetate, and (E)-2-nonenal stimulated [Ca2]i mobilization in human neutrophils, with the most potent being geranylacetone (EC50 = 7.6 ± 1.9 µM) and isobornyl acetate 6.4 ± 1.7 (EC50 = 7.6 ± 1.9 µM). In addition, treatment of neutrophils with β-pinene, sabinene, γ-terpinene, geranylacetone, and isobornyl acetate desensitized the cells to N-formyl-Met-Leu-Phe (fMLF)- and interleukin-8 (IL-8)-induced [Ca2]i flux and inhibited fMLF-induced chemotaxis. The effects of β-pinene, sabinene, γ-terpinene, geranylacetone, and isobornyl acetate on neutrophil [Ca2+]i flux were inhibited by transient receptor potential (TRP) channel blockers. Furthermore, the most potent compound, geranylacetone, activated Ca2+ influx in TRPV1-transfected HEK293 cells. In contrast, myristicin inhibited neutrophil [Ca2+]i flux stimulated by fMLF and IL-8 and inhibited capsaicin-induced Ca2+ influx in TRPV1-transfected HEK293 cells. These findings, as well as pharmacophore modeling of TRP agonists, suggest that geranylacetone is a TRPV1 agonist, whereas myristicin is a TRPV1 antagonist. Thus, at least part of the medicinal properties of Ferula essential oils may be due to modulatory effects on TRP channels.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents

Schepetkin

Кушнаренко

Özek

et al. 2016

J. Agric. Food Chem.

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“…Monoterpenes are inexpensive raw material extracted from biomass and are extensively employed on the production of more added value chemicals and new drugs intermediates [3][4][5].…”

Section: Introductionmentioning

confidence: 99%

Tin-Catalyzed Urea Alcoholysis With β-Citronellol: A Simple and Selective Synthesis of Carbamates

Chaves

Silva

2016

Catal Lett

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Tin(II) chloride is a stable and water tolerant Lewis acid, commercially available and less corrosive than Brønsted acid catalysts. Our proposal was demonstrated that SnCl 2 was an efficient catalyst on the urea alcoholysis with b-citronellol. We investigated the effects of main reaction parameters such as concentration and tin(II) catalyst nature, reagents stoichiometry and reaction temperature. In homogenous conditions with DMSO as solvent, the SnCl 2 -catalyzed urea alcoholysis reactions under air flux achieved high conversion and selectivity for b-citronellyl carbamate (ca. 90 and 95 %, respectively). Among tin(II) catalysts assessed, SnCl 2 was more active due to its total solubility. Possible intermediates of active Sn(II) species were discussed based on the results of catalytic runs and FT-IR spectroscopy measurements of the liquid phase after the reaction. FT-IR spectroscopy data showed that the active species could be a complex of a Sn(II) atom coordinated with N=C=O. This novel and phosgene-free selective process provide an inexpensive and attractive route to synthesize terpenic carbamates through inexpensive and renewable reactant (i.e. urea). Moreover, SnCl 2 was also an efficient catalyst on synthesis of b-citronellyl carbonate. Graphical AbstractOH -citronellol H 2 N NH 2 O Urea + SnCl 2 DMSO Air flow O NH 2 O -citronellyl Carbamate NH 3 + Ammonia β 0 3 0 6 0 9 0 0 20 40 60 80 100 (%) Time (min) β -Citronellol Conversion Selectivity β-Citronellyl Carbamate β

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“…209 Similarly, thymol derivatives, here exemplified by compound 53, are true TRPM8 antagonists, but as for most phytochemicals with TRPM8 activity, also display strong TRPA1 modulation.…”

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confidence: 99%

Transient Receptor Potential Melastatin 8 Channel (TRPM8) Modulation: Cool Entryway for Treating Pain and Cancer

et al. 2016

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Abstract. TRPM8 ion channels, the primary cold sensors in humans, are activated by innocuous cooling (< 28 ºC) and cooling compounds (menthol, icilin), and are implicated in sensing unpleasant cold stimuli, as well as in mammalian thermoregulation. Over-expression of these thermoregulators in prostate cancer and in other life-threatening tumors, along with their contribution to an increasing number of pathological conditions, opens a plethora of medicinal chemistry opportunities to develop receptor modulators. This Perspective seeks to compile current known modulators for this ion channel, since both agonists and antagonists may be useful for the treatment of most TRPM8-mediated pathologies. We primarily focus on SAR data for the different families of compounds and the pharmacological properties of the most promising ligands. Furthermore, we also address the knowledge about the channel structure, although still in its infancy, and the role of the TRPM8 protein signalplex to channel function and dysfunction. We finally outline the potential future prospects of the challenging TRPM8 drug discovery field.

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Effect of acyclic monoterpene alcohols and their derivatives on TRP channels

Cited by 20 publications

References 46 publications

Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents

Modulation of Human Neutrophil Responses by the Essential Oils from Ferula akitschkensis and Their Constituents

Tin-Catalyzed Urea Alcoholysis With β-Citronellol: A Simple and Selective Synthesis of Carbamates

Transient Receptor Potential Melastatin 8 Channel (TRPM8) Modulation: Cool Entryway for Treating Pain and Cancer

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