Characterization of in vitro metabolism of capsazepine, a vanilloid transient receptor potential channel antagonist, by liquid chromatography quadrupole ion trap mass spectrometry

2011 ◽  
Vol 25 (4) ◽  
pp. 479-492 ◽  
Author(s):  
Jennifer Douat ◽  
Pascal Vachon ◽  
Francis Beaudry
Keyword(s):  
Mass Spectrometry ◽  
Transient Receptor Potential ◽  
Ion Trap ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Quadrupole Ion Trap ◽  
Ion Trap Mass Spectrometry ◽  
Transient Receptor

scholarly journals Design, Synthesis and In Vitro Experimental Validation of Novel TRPV4 Antagonists Inspired by Labdane Diterpenes

Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 519
Author(s):  
Sarah Mazzotta ◽  
Gabriele Carullo ◽  
Aniello Schiano Moriello ◽  
Pietro Amodeo ◽  
Vincenzo Di Marzo ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Calcium Influx ◽  
Biological Activities ◽  
Receptor Potential ◽  
Transient Receptor Potential Channel ◽  
Design Synthesis ◽  
Cellular Assays ◽  
Transient Receptor ◽  
Trpv4 Channel

Labdane diterpenes are widespread classes of natural compounds present in variety of marine and terrestrial organisms and plants. Many of them represents “natural libraries” of compounds with interesting biological activities due to differently functionalized drimane nucleus exploitable for potential pharmacological applications. The transient receptor potential channel subfamily V member 4 (TRPV4) channel has recently emerged as a pharmacological target for several respiratory diseases, including the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Inspired by the labdane-like bicyclic core, a series of homodrimane-derived esters and amides was designed and synthesized by modifying the flexible tail in position 1 of (+)-sclareolide, an oxidized derivative of the bioactive labdane-type diterpene sclareol. The potency and selectivity towards rTRPV4 and hTRPV1 receptors were assessed by calcium influx cellular assays. Molecular determinants critical for eliciting TRPV4 antagonism were identified by structure-activity relationships. Among the selective TRPV4 antagonists identified, compound 6 was the most active with an IC50 of 5.3 μM. This study represents the first report of semisynthetic homodrimane TRPV4 antagonists, selective over TRPV1, and potentially useful as pharmacological tools for the development of novel TRPV4 channel modulators.

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