Stomach cancer this year is estimated to affect 27,510 patients and just over 40% of these patients will die. Based on these statistics, a therapeutic lead is needed to prevent the formation of stomach cancer rather than waiting until it develops and treating it. N-methyl-N-nitrosourea (NMU) is formed in situ in the gut from the intake of foods containing nitrate preservatives. At low pH, NMU decomposes to a methyl diazonium salt that specifically alkylates guanine at the O-6 position. This alkylation of guanine on existing DNA leads to DNA mispairing mutations that are linked to stomach cancer. NMU was successfully synthesized and the reaction conditions for the treatment of N-methylurea with other substrates were optimized. Reaction conditions were developed to determine the effect of dietary supplements, vitamins, and flavonoids on the extent of guanine alkylation by NMU. The alkylation of guanine was shown to be successful by HPLC analysis. A HPLC protocol to detect guanine and O-6 methyl guanine standard was optimized. Thus far, ascorbic acid (Vitamin C) has shown effective inhibition of alkylation and Vitamin E has no effect on the alkylation of guanine. Each supplement is compared to the control under the same reaction conditions. Modification of methylation conditions with NMU and results with other flavones and flavonoids will be reported. Relative amounts of inhibition will be reported based on concentrations. These results will provide a lead compound that in the future will form the basis for new the design and synthesis of new compounds.

Inhibiting nistroso related methylation of guanine using dietary supplements and flavonoids

ACS Spring Meeting 2021

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