Dichloroethyl carbamoyl ester of delta-9-tetrahydrocannabinol. Chemical synthesis and biological testing and evaluation as a potentially site-specific anti-tumor agent.

Abstract

A novel compound, Delta-9-Tetrahydrocannabinol Nitrogen Mustard (THC-mustard), was chemically synthesized and characterized. The rationale was to target a known anti-tumor agent, nitrogen mustard, to tumor cells with "THC Receptors" and/or "Estrogen Receptors". A microtest in vitro bioassay was designed and developed to compare the ID50 of the drug in cell culture against various tumor cell types. The ID50's of the THC-mustard were determined against several tumor cell types in culture, compared with Mechlorethamine HCl, Delta-9-Tetrahydrocannabinol (THC), and an equimolar mixture of THC and nitrogen mustard. A preliminary toxicity study by the NCI of the THC-mustard (in vivo) in Swiss male mice bearing the P388 tumor (1 dose X 1 day) by the I.P. route was also carried out. A description of the rationale, chemical synthesis and characterization, bioassay, and results is herewith presented.