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: Erin Joseph, Julie L Eiseman, Diana S Hamilton, Haibo Wang, Heekyung Tak, Zhebo Ding, Bruce Ganem, Donald J Creighton
• Journal: Journal of medicinal chemistry (J Med Chem) Vol. 46 Issue 1 Pg. 194-6 (Jan 02 2003) ISSN: 0022-2623 [Print] United States
• PMID: 12502374 (Publication Type: Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Antineoplastic Agents
• Crotonates
• Cyclohexanes
• Cyclohexanones
• Cycloparaffins
• 2-crotonyloxymethyl-2-cyclohexenone
• Glutathione

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, chemistry, pharmacology)
• Cell Division (drug effects)
• Crotonates (chemical synthesis, chemistry, pharmacology)
• Cyclohexanes (chemical synthesis, chemistry, pharmacology)
• Cyclohexanones (chemical synthesis, chemistry, pharmacology)
• Cycloparaffins (chemical synthesis, chemistry, pharmacology)
• Glutathione (chemistry, metabolism)
• Mice
• Structure-Activity Relationship
• Tumor Cells, Cultured