Planta Med 2012; 78 - P_26
DOI: 10.1055/s-0032-1307534

Bioactive Products from Singlet Oxygen Photooxygenation of Δ9-THC, Δ8-THC, And Δ9-THC-Acid-A

A Galal 1, MM Radwan 1, S Ahmed 2, D Slade 1, W Gul 3, SI Khan 1, 4, S Ross 1, 4, MA ElSohly 1, 3, 5
  • 1National Center for Natural Products Research, School of Pharmacy, the University of Mississippi, University, MS 38677, USA
  • 2Faculty of Pharmacy, Suez Canal University, Ismailia, Egypt
  • 3ElSohly Laboratories, Inc. Industrial Park Drive, Oxford, MS, 38655, USA
  • 4Department of Pharmacognosy
  • 5Department of Pharmaceutics, School of Pharmacy, the University of Mississippi, University, MS 38677, USA

The objective of this project was to utilize the singlet oxygen photooxygenation of Δ9-THC, Δ8-THC, and Δ9-THC-Acid-A as a potential sustainable source to provide minor cannabinoid metabolites in sufficient quantities for further studies. This reaction afforded 16 new oxygenated derivatives, in addition to previously isolated or identified compounds. The new products were evaluated for their in vitro anticancer, antimicrobial, antimalarial, and antileishmanial activities. Compounds 1 and 2 displayed anticancer activity against SK-MEL, BT-549, and SK-OV-3 cell lines with IC50 values of 5.7, 5.3, and >10µg/mL, respectively for 1 and 5.0, 4.2, and 4.4µg/mL, respectively for 2. Compound 3 showed less anticancer activity (8.5µg/mL) against SK-MEL cell line, while 4 was inactive. A significant anticryptococcal effect, equal to that of amphotericin B was attributed to 2, 3, and 4, with MIC of 2.50µg/mL. Additionally, Δ8-THC quinone (2) exhibited antimalarial effect with IC50 of 0.16 and 0.20µg/mL against chloroquine-sensitive and chloroquine-resistant clones of P. falciparum, respectively, and antileishmanial activity with IC50/IC90 of 0.06/0.13µg/mL which is stronger than that of amphotericin B.

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Acknowledgments: The project described was supported in part by Grant No. 5P20RR021929 from the National Center for Research Resource and grant no. N01DA-05–7746 from NIDA.