Molecular basis of the antitumor activities of 2-crotonyloxymethyl-2-cycloalkenones.
The antitumor activity of 2-crotonyloxymethyl-2-cyclohexenone (COMC-6) is not the result of the GSH conjugate (GSMC-6) formed inside tumor cells, as the diethyl ester prodrug form of GSMC-6 displays little antitumor activity with B16 melanotic melanoma in vitro (IC(50) > 460 microM) versus COMC-6 (IC(50) 0.041 microM) and its five- and seven-membered ring homologues. Antitumor activity probably results from a reactive intermediate that forms during conjugation of the COMCs with intracellular GSH.
Joseph
Erin
E
Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA.
Eiseman
Julie L
JL
Hamilton
Diana S
DS
Wang
Haibo
H
Tak
Heekyung
H
Ding
Zhebo
Z
Ganem
Bruce
B
Creighton
Donald J
DJ
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003437:Crotonates / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003510:Cyclohexanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D003512:Cyclohexanones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D003516:Cycloparaffins / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D005978:Glutathione / Q000737:chemistry / Q000378:metabolism; D051379:Mice; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D003437:Crotonates; D003510:Cyclohexanes; D003512:Cyclohexanones; D003516:Cycloparaffins; C073431:2-crotonyloxymethyl-2-cyclohexenone; D005978:Glutathione