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Galal Osman A , Elokely KM , Yadav VK , Carvalho P , Radwan M , Slade D , Gul W , Khan S , Dale OR , Husni AS , Klein ML , Cutler SJ , Ross SA , ElSohly MA
Bioactive products from singlet oxygen photooxygenation of cannabinoids
Eur J Med Chem. 2018 Jan 1;143 :983-996
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Abstract
Photooxygenation of Delta(8) tetrahydrocannabinol (Delta(8)-THC), Delta(9) tetrahydrocannabinol (Delta(9)-THC), Delta(9) tetrahydrocannabinolic acid (Delta(9)-THCA) and some derivatives (acetate, tosylate and methyl ether) yielded 24 oxygenated derivatives, 18 of which were new and 6 were previously reported, including allyl alcohols, ethers, quinones, hydroperoxides, and epoxides. Testing these compounds for their modulatory effect on cannabinoid receptors CB1 and CB2 led to the identification of 7 and 21 as CB1 partial agonists with Ki values of 0.043 muM and 0.048 muM, respectively and 23 as a cannabinoid with high binding affinity for CB2 with Ki value of 0.0095 muM, but much less affinity towards CB1 (Ki 0.467 muM). The synthesized compounds showed cytotoxic activity against cancer cell lines (SK-MEL, KB, BT-549, and SK-OV-3) with IC50 values ranging from 4.2 to 8.5 mug/mL. Several of those compounds showed antimicrobial, antimalarial and antileishmanial activities, with compound 14 being the most potent against various pathogens.
Notes
1768-3254 Galal Osman, Ahmed Elokely, Khaled M Yadav, Vivek K Carvalho, Paulo Radwan, Mohamed Slade, Desmond Gul, Waseem Khan, Shabana Dale, Olivia R Husni, Afeef S Klein, Michael L Cutler, Stephen J Ross, Samir A ElSohly, Mahmoud A Journal Article France Eur J Med Chem. 2018 Jan 1;143:983-996. doi: 10.1016/j.ejmech.2017.11.043. Epub 2017 Nov 21.