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HU-446 and HU-465, Derivatives of the Non-psychoactive Cannabinoid Cannabidiol, Decrease the Activation of
Ewa Kozela1, Christeene Haj2, Lumir Hanuš2
1The Dr Miriam and Sheldon G. Adelson Center for the Biology of Addictive Diseases, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, 69978, Israel.
Chemical Biology & Drug Design
|August 12, 2015
Summary
New cannabidiol (CBD) derivatives, HU-446 and HU-465, reduce inflammation in models of multiple sclerosis (MS). These compounds inhibit T cell proliferation and IL-17 release, suggesting potential for autoimmune disease treatment.
Area of Science:
- Neuroimmunology
- Pharmacology
- Immunology
Background:
- Cannabidiol (CBD) demonstrates anti-inflammatory effects in experimental autoimmune encephalomyelitis (EAE), a model for multiple sclerosis (MS).
- Novel synthetic derivatives of CBD, HU-446 (natural (-)-CBD derivative) and HU-465 (synthetic (+)-CBD derivative), were synthesized for enhanced therapeutic potential.
Purpose of the Study:
- To investigate the anti-inflammatory effects of HU-446 and HU-465 on myelin oligodendrocyte glycoprotein (MOG)-specific T cells.
- To elucidate the mechanism of action of these CBD derivatives, including their receptor binding affinities and effects on T cell activation.
Main Methods:
- Binding assays and molecular modeling were used to determine receptor affinities of HU-446 and HU-465.
- In vitro studies assessed the impact of HU-446 and HU-465 on MOG35-55-induced proliferation and IL-17 release from T cells.
Main Results:
- HU-446 showed negligible affinity for CB1 and CB2 receptors, while HU-465 exhibited high nanomolar affinity.
- Both HU-446 and HU-465 inhibited MOG35-55-induced T cell proliferation and IL-17 release via CB1/CB2 receptor-independent pathways at concentrations of 5 and 10 μm.
Conclusions:
- HU-446 and HU-465 possess significant anti-inflammatory properties.
- These novel CBD derivatives demonstrate potential as therapeutic agents for inflammatory and autoimmune diseases, independent of cannabinoid receptor modulation.
