The antitumor activity of 2-crotonyloxymethyl-2-cyclohexenone (COMC-6) is not the result ofthe GSH conjugate (GSMC-6) formed inside tumor cells, as the diethyl ester prodrug form ofGSMC-6 displays little antitumor activity with B16 melanotic melanoma in vitro (IC50> 460μM) versus COMC-6 (IC50 0.041 μM) and its five- and seven-membered ring homologues.Antitumor activity probably results from a reactive intermediate that forms during conjugationof the COMCs with intracellular GSH.
