Synthesis and antitumor activity of quinonoid derivatives of cannabinoids.
Journal of medicinal chemistry 2004 Jul 15; 47(15):3800-6
Kogan N NM, Rabinowitz R R, Levi P P, Gibson D D, Sandor P P, Schlesinger M M, Mechoulam R R
Department of Medicinal Chemistry and Natural Products, School of Pharmacy, The Hebrew University, Jerusalem 91120, Israel.
Three cannabis constituents, cannabidiol (1), Delta(8)-tetrahydrocannabinol (3), and cannabinol (5), were oxidized to their respective para-quinones 2, 4, and 6. In the 1960s, the oxidized product 4 had been assigned a para-quinone structure, which was later modified to an ortho-quinone. To distinguish between the two possible quinone structures, a detailed NMR investigation was undertaken. The original para-quinone structure was confirmed. X-ray crystallography elucidated the structures of the crystalline 2 and 6. All three compounds displayed antiproliferative activity in several human cancer cell lines in vitro, and quinone 2 significantly reduced cancer growth of HT-29 cancer in nude mice.