Novel Synthesis of C-Methylated Phytocannabinoids Bearing Anti-inflammatory Properties

Yarden Lavi, Natalya M. Kogan*, Louise M. Topping, Caojie Liu, Fiona E. McCann, Richard O. Williams, Aviva Breuer, Zhanna Yekhtin, Aviva Friedman Ezra, Ruth Gallily, Marc Feldmann, Raphael Mechoulam

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

There is growing interest in non-psychoactive phytocannabinoids, namely cannabidiol (CBD), cannabigerol (CBG), and cannabichromene, as potential leads for novel therapeutic agents. In this study, we report on the development of new derivatives in which we methylated either position 4 of olivetol or the phenolic positions of olivetol, or both. We introduce a refinement on previously reported chemical procedures for phytocannabinoid derivatization as well as the biological evaluation of all derivatives in anti-inflammatory in vivo models. Compounds such as the CBD derivative, 2 and the CBG derivative, 11, significantly reduced cytokine levels when compared to their parent compounds. Moreover, both of these derivatives proved to be as potent as dexamethasone for the inhibition of IL-1β. We believe that these new derivatives, as described herein, can be further developed as novel drug candidates for inflammatory conditions.

Original languageAmerican English
Pages (from-to)5536-5549
Number of pages14
JournalJournal of Medicinal Chemistry
Volume66
Issue number8
DOIs
StatePublished - 27 Apr 2023

Bibliographical note

Publisher Copyright:
© 2023 The Authors. Published by American Chemical Society

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