Potential radiosensitizing agents. Dinitroimidazoles

Authors:
  • KAKrishna C. Agrawal
    Krishna C. Agrawal
  • KBKathleen B. Bears
    Kathleen B. Bears
  • RSRaj K. Sehgal
    Raj K. Sehgal
  • JBJoe N. Brown
    Joe N. Brown
  • PRPatricia E. Rist
    Patricia E. Rist
  • WRW. D. Rupp
    W. D. Rupp
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Abstract
New compounds of the nitroimidazole series have been synthesized as radiosensitizers which selectively sensitize hypoxic cells to the lethal effect of radiation. The reaction of 2,4(5)-dinitroimidazole (2) with chloroethanol or hydrochloric acid yielded 4(5)-nitro-5(4)-chloroimidazole (3), which upon reaction with ethylene oxide yielded the 4-nitro-5-chloroimidazole-1-ethanol (6). Reaction of 2 with ethylene oxide resulted in a mixture of two compounds, the 2,4-dinitroimidazole-1-ethanol (4) and 2,3-dihydro-5-nitroimidazo[2,1-b]oxazole (5). The structure of the new heterocyclic compound 5 was confirmed by 1H NMR, mass spectrum, and X-ray crystallography. These agents were tested for their ability to sensitize hypoxic Escherichia coli cells to killing by ionizing radiation. Compound 4 was found to be the most active agent of this series of compounds.