title: Antibacterial cannabinoids from Cannabis sativa: a structure-activity study.
abstract: Marijuana (Cannabis sativa) has long been known to contain antibacterial cannabinoids, whose potential to address antibiotic resistance has not yet been investigated. All five major cannabinoids (cannabidiol (1b), cannabichromene (2), cannabigerol (3b), Delta (9)-tetrahydrocannabinol (4b), and cannabinol (5)) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance. Activity was remarkably tolerant to the nature of the prenyl moiety, to its relative position compared to the n-pentyl moiety (abnormal cannabinoids), and to carboxylation of the resorcinyl moiety (pre-cannabinoids). Conversely, methylation and acetylation of the phenolic hydroxyls, esterification of the carboxylic group of pre-cannabinoids, and introduction of a second prenyl moiety were all detrimental for antibacterial activity. Taken together, these observations suggest that the prenyl moiety of cannabinoids serves mainly as a modulator of lipid affinity for the olivetol core, a per se poorly active antibacterial pharmacophore, while their high potency definitely suggests a specific, but yet elusive, mechanism of activity.
authors.affiliation: Dipartimento di Scienze Chimiche, Alimentari, Farmaceutiche e Farmacologiche, Università del Piemonte Orientale, 28100 Novara, Italy. appendino@pharm.unipmn.it
authors.forename: Giovanni
authors.initials: G
authors.lastname: Appendino
authors.forename: Simon
authors.initials: S
authors.lastname: Gibbons
authors.forename: Anna
authors.initials: A
authors.lastname: Giana
authors.forename: Alberto
authors.initials: A
authors.lastname: Pagani
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Grassi
authors.forename: Michael
authors.initials: M
authors.lastname: Stavri
authors.forename: Eileen
authors.initials: E
authors.lastname: Smith
authors.forename: M Mukhlesur
authors.initials: MM
authors.lastname: Rahman
mesh_terms: D000107:Acetylation; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002186:Cannabinoids / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002188:Cannabis / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D016106:Methicillin Resistance; D008745:Methylation; D008826:Microbial Sensitivity Tests; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet; D013211:Staphylococcus aureus / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D000900:Anti-Bacterial Agents; D002186:Cannabinoids