5-(Halomethyl)uridine derivatives as potential antitumor radiosensitizers: A DFT study

Abstract Considering the fact that the efficiency of the uridine-5-methyl radical in producing cytotoxic DNA intrastrand cross-link lesions is greatly higher than that of the uridine-5-yl radical, the radiosensitizing action of 5-(halomethyl)uridines (5-XCH 2 U, X = F, Cl, or Br) is studied in the present work. It is found that 5-XCH 2 U has sufficient electron affinity to capture a pre-hydrated or a hydrated electron, and electron attachment leads to significantly facile X − elimination forming the uridine-5-methyl radical. All these three halogenated uridine derivatives are shown to be potential radiosensitizers, with their radiosensitizing abilities increased in an order 5-FCH 2 U  2 U ≈ 5-BrCH 2 U.