“Chemical
Basis for the Anti-Tumor Toxicity of Crotonyloxymethyl-1,4-“
John Jackson, Biochemistry, UMBC, 1000 Hilltop
Circle, Baltimore, MD 21250
Don Creighton,
Ph.D., Department of Chemistry and Biochemistry, UMBC,
1000 Hilltop Circle, Baltimore, MD 21250
The goal of this research is to test the ability of a class of compounds known as benzoquinones to selectively inhibit the growth of breast cancer tissue. Our lab hypothesizes that substituted benzoquinones are catalyzed to a highly reactive form by glutathione transferase (GST). Because GST is over-expressed in breast cancer cells, substituted benzoquinones should be selectively toxic for breast cancer tissue.
The aims of my project
are 1) To synthesize the crotonate ester of 2-(hydroxymethyl)-1,4 benzoquinone
(product is henceforth called “1"; 2) To determine the ability
of p glutathione transferase (p GST) to catalyze the conversion of 1 to
the corresponding exocyclic enone in the presence of glutathione (GSH);
3) To determine how the exocyclic enone partitions among different possible
adducts of glutathione; 4) To test the ability of 1 to form DNA adducts
in the presence of glutathione and p GST; 5) To test for correlations
between the amount of p GST expressed in different types of tumor cells
in tissue culture, and the cytotoxicity of 1.
The identification and relative amounts of the possible product species
will be determined by a combination of NMR and mass spectrometry. The
toxicity of 1 and the exocyclic enone will be tested for different tumor
cell cultures, which differ in the amount of GST they express. Our findings
should elucidate whether or not the toxicity of 1 involves a GST dependent
mechanism.
