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Keywords = phytoquinones

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14 pages, 2633 KiB  
Article
The Impact of a Quinone Scaffold on Thermo-TRPs Modulation by Dimethylheptyl Phytocannabinoids
by Aniello Schiano Moriello, Aurora Bossoni, Daiana Mattoteia, Diego Caprioglio, Alberto Minassi, Giovanni Appendino, Luciano De Petrocellis, Pietro Amodeo and Rosa Maria Vitale
Int. J. Mol. Sci. 2025, 26(6), 2682; https://doi.org/10.3390/ijms26062682 - 17 Mar 2025
Viewed by 641
Abstract
Phytocannabinoids (pCBs) from Cannabis sativa represent an important class of bioactive molecules, potentially useful for the treatment of a wide range of diseases. Their efficacy is due to their ability to interact with multiple targets of the endocannabinoid system, including the thermosensitive transient [...] Read more.
Phytocannabinoids (pCBs) from Cannabis sativa represent an important class of bioactive molecules, potentially useful for the treatment of a wide range of diseases. Their efficacy is due to their ability to interact with multiple targets of the endocannabinoid system, including the thermosensitive transient receptor potential (Thermo-TRPs), namely TRPV1-4, TRPA1, and TRPM8 channels. Previously, we demonstrated a shift in selectivity toward TRPA1 in the activity profile of the main pCBs, that is, CBD, ∆8-THC, CBG, CBC, and CBN, by swapping the pentyl chain with the α,α-dimethylheptyl (DMH) one. Using these derivatives as a starting point, here we investigate the effects on the thermo-TRPs activity profile of the integration of a quinone group into the resorcinol scaffold. We found that, while the activity on TRPA1 is substantially retained, an increase in potency/efficacy on the TRPV3 modulation is observed. Docking studies were used to elucidate the binding modes of the most active compounds toward this receptor, providing a rationale for this biological activity. In summary, we show that the quinone derivatives of DMH-pCBs are endowed with a TRPA1/TRPV3 desensitizing activity, potentially useful for the treatment of skin diseases sustained by inflammatory conditions. Full article
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