Synthesis and Antitumor Activity of Quinonoid Derivatives of Cannabinoids

Abstract

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.

HU-331, a novel cannabinoid-based anticancer topoisomerase II inhibitor

“…(+)-HU-331 was synthesized from (+)-CBD by the same method as HU-331 from (À)-CBD (8). The level of cell death of (+)-HU-331 did not significantly differ from that observed with HU-331 (Fig.…”

“…(+)-HU-331 was synthesized as previously described for (À)-HU-331 (8), and its ability to mediate Jurkat cell death was assayed by MTT test as described above. The assay was carried out in two repeated experiments.…”

“…The following compounds were added 15 min before HU-331: superoxide dismutase mimic (20,8, and 4 mmol/L) for a positive control, or 0.5% ethanol for a negative control. Three hours after the compound addition, the cells were centrifuged, and the supernatants were frozen at À70jC until use.…”

“…It showed very high efficacy against human cancer cell lines in vitro and against in vivo grafts of human tumors in nude mice (8).…”

Recent advances in 1,4-benzoquinone chemistry

“…129 Cannabidiol (101) has been oxidized by air in an alcoholic solution in the presence of 5% KOH over 24 h at 0 °C to hydroxyquinone (102) at ca. 20% yield.…”