title: Molecular basis of the antitumor activities of 2-crotonyloxymethyl-2-cycloalkenones.
abstract: 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.
authors.affiliation: Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA.
authors.forename: Erin
authors.initials: E
authors.lastname: Joseph
authors.forename: Julie L
authors.initials: JL
authors.lastname: Eiseman
authors.forename: Diana S
authors.initials: DS
authors.lastname: Hamilton
authors.forename: Haibo
authors.initials: H
authors.lastname: Wang
authors.forename: Heekyung
authors.initials: H
authors.lastname: Tak
authors.forename: Zhebo
authors.initials: Z
authors.lastname: Ding
authors.forename: Bruce
authors.initials: B
authors.lastname: Ganem
authors.forename: Donald J
authors.initials: DJ
authors.lastname: Creighton
mesh_terms: 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
chemical_list: D000970:Antineoplastic Agents; D003437:Crotonates; D003510:Cyclohexanes; D003512:Cyclohexanones; D003516:Cycloparaffins; C073431:2-crotonyloxymethyl-2-cyclohexenone; D005978:Glutathione