TY - JOUR
T1 - Antibacterial cannabinoids from Cannabis sativa
T2 - A structure-activity study
AU - Appendino, Giovanni
AU - Gibbons, Simon
AU - Giana, Anna
AU - Pagani, Alberto
AU - Grassi, Gianpaolo
AU - Stavri, Michael
AU - Smith, Eileen
AU - Rahman, M. Mukhlesur
PY - 2008/8
Y1 - 2008/8
N2 - 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 (lb), cannabichromene (2), cannabigerol (3b), Δ9-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.
AB - 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 (lb), cannabichromene (2), cannabigerol (3b), Δ9-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.
UR - http://www.scopus.com/inward/record.url?scp=51849131485&partnerID=8YFLogxK
U2 - 10.1021/np8002673
DO - 10.1021/np8002673
M3 - Article
SN - 0163-3864
VL - 71
SP - 1427
EP - 1430
JO - Journal of Natural Products
JF - Journal of Natural Products
IS - 8
ER -