Molecular basis of the antitumor activities of 2-crotonyloxymethyl-2-cycloalkenones

  • J Med Chem. 2003 Jan 2;46(1):194-6. doi: 10.1021/jm0203027.
Erin Joseph  1 ,  Julie L Eiseman ,  Diana S Hamilton ,  Haibo Wang ,  Heekyung Tak ,  Zhebo Ding ,  Bruce Ganem ,  Donald J Creighton
Affiliations
  • 1. Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, Baltimore, Maryland 21250, USA.
PMID: 12502374 DOI: 10.1021/jm0203027
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.

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