Synthesis and antitumor activity of quinonoid derivatives of cannabinoids

J Med Chem. 2004 Jul 15;47(15):3800-6. doi: 10.1021/jm040042o.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cannabinoids / chemical synthesis*
  • Cannabinoids / chemistry
  • Cannabinoids / pharmacology
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Humans
  • Magnetic Resonance Spectroscopy
  • Mice
  • Mice, Nude
  • Quinones / chemical synthesis*
  • Quinones / chemistry
  • Quinones / pharmacology
  • Structure-Activity Relationship
  • Transplantation, Heterologous

Substances

  • Antineoplastic Agents
  • Cannabinoids
  • Quinones