Cannabidiol-2',6'-Dimethyl Ether, a Cannabidiol Derivative, Is a Highly Potent and Selective 15-Lipoxygenase Inhibitor.Takeda S, Usami N, Yamamoto I, Watanabe K
Drug Metab Dispos 2009 Apr 30.
The inhibitory effect of nordihydroguaiaretic acid (NDGA), a non-selective lipoxygenase (LOX) inhibitor, -mediated 15-LOX inhibition has been reported to be affected by modification of its catechol ring such as methylation of the hydroxyl group. Cannabidiol (CBD), one of the major components of marijuana, is known to inhibit LOX activity. Based on the phenomenon observed in NDGA, we investigated whether or not methylation of CBD affects its inhibitory potential against 15-LOX, since CBD contains a resorcinol ring, which is an isomer of catechol. Although CBD inhibited 15-LOX activity with an IC50 value (50% inhibition concentration) of 2.56 microM, its mono-methylated and di-methylated derivatives, CBD-2'-monomethyl ether (CBDM) and CBD-2',6'-dimethyl ether (CBDD) inhibited 15-LOX activity more strongly than CBD. The number of methyl groups in the resorcinol moiety of CBD (as a prototype) appears to be a key determinant for potency and selectivity in inhibition of 15-LOX. The IC50 value of 15-LOX inhibition by CBDD is 0.28 microM, and the inhibition selectivity for 15-LOX (i.e., the 5-LOX/15-LOX ratio of IC50 values) is more than 700. Among LOX isoforms, 15-LOX is known to be able to oxygenate the cholesterol esters in the low density lipoprotein (LDL) particle (i.e., the formation of oxidized LDL). Thus, 15-LOX is suggested to be involved in developing atherosclerosis, and CBDD may be a useful prototype for producing medicines for atherosclerosis.
Source: Unbound MEDLINE | Cannabidiol-2',6'-Dimethyl Ether, a Cannabidiol Derivative, Is a Highly Potent and Selective 15-Lipoxygenase Inhibitor. PubMed Journal article abstract