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Bioactive products from singlet oxygen photooxygenation of cannabinoids

Bioactive products from singlet oxygen photooxygenation of cannabinoids

Authors :
Waseem Gul
Olivia R. Dale
Michael L. Klein
Shabana I. Khan
Mohamed M. Radwan
Afeef S. Husni
Mahmoud A. ElSohly
Vivek K. Yadav
Desmond Slade
Paulo Sèrgio De Carvalho
Samir A. Ross
Stephen J. Cutler
Ahmed Galal Osman
Khaled M. Elokely
Source :
European Journal of Medicinal Chemistry. 143:983-996
Publication Year :
2018
Publisher :
Elsevier BV, 2018.

Abstract

Photooxygenation of Δ8 tetrahydrocannabinol (Δ8-THC), Δ9 tetrahydrocannabinol (Δ9-THC), Δ9 tetrahydrocannabinolic acid (Δ9-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 μM and 0.048 μM, respectively and 23 as a cannabinoid with high binding affinity for CB2 with Ki value of 0.0095 μM, but much less affinity towards CB1 (Ki 0.467 μM). 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 μg/mL. Several of those compounds showed antimicrobial, antimalarial and antileishmanial activities, with compound 14 being the most potent against various pathogens.

Details

ISSN :
02235234
Volume :
143
Database :
OpenAIRE
Journal :
European Journal of Medicinal Chemistry
Accession number :
edsair.doi.dedup.....204b775f5e3a521d99f00e8bfab390a4
Full Text :
https://doi.org/10.1016/j.ejmech.2017.11.043