New cannabidiol derivatives: synthesis, binding to cannabinoid receptor, and evaluation of their antiinflammatory activity.
Cannabidiol (CBD) and cannabidiol dimethyl hephtyl (CBD-DMH) were hydrogenated to give four different epimers. The new derivatives were evaluated for their ability to modulate the production of reactive oxygen intermediates (ROI), nitric oxide (NO), and tumor necrosis factor (TNF-alpha) by murine macrophages, and for their binding to the cannabinoid receptor (CB(1)). Surprisingly, we found that these derivatives exhibit good binding to CB(1). In addition hydrogenated CBD and CBD-DMH demonstrate bioactivities different from their original compounds.
Ben-Shabat
Shimon
S
Department of Pharmacology and School of Pharmacy, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel. sbs@bgu.ac.il
Hanus
Lumír O
LO
Katzavian
Galia
G
Gallily
Ruth
R
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000138:chemical synthesis* / Q000494:pharmacology; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D002185:Cannabidiol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D002460:Cell Line; D066298:In Vitro Techniques; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009569:Nitric Oxide / Q000096:biosynthesis; D011869:Radioligand Assay; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D043884:Receptor, Cannabinoid, CB1 / Q000378:metabolism*; D013329:Structure-Activity Relationship; D013574:Synaptosomes / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
D000894:Anti-Inflammatory Agents, Non-Steroidal; D017382:Reactive Oxygen Species; D043884:Receptor, Cannabinoid, CB1; D014409:Tumor Necrosis Factor-alpha; D002185:Cannabidiol; D009569:Nitric Oxide