Mechanism of action of the nitrosoureas-II. Formation of fluoroethylguanosine from the reaction of bis-fluoroethyl nitrosourea and guanosine

The haloethyl nitrosoureas evidently decompose in neutral aqueous solution to generate haloethyl carbonium ions. In support of this hypothesis, we have shown that bis-fluoroethyl nitro-sourea (BFNU) reacts with guanosine to generate 7-β-fluoroethylguanosine, in addition to larger amounts of 7-β-hydroxyethylguanosine. This nucleoside analog has been synthesized from guanosine and fluorobromoethane, and identified in a BFNU-guanosine reaction mixture by high pressure liquid chromatography. Fluoroethylguanosine, per se, has an antitumor effect against P-388 murine leukemia, suggesting that it may have some role in mediating the antitumor or toxic effects of BFNU.