In vitro fluorine-19 nuclear magnetic resonance study of the liberation of antitumor nitrogen mustard from prodrugs

Abstract

The syntheses of two novel glucuronide prodrugs of nitrogen mustard with a fluorine tag are reported. These prodrugs, which differ only by the presence or not of a spacer, were designed for selective activation in the necrotic area of tumors by β-glucuronidase. Kinetics of enzymatic hydrolysis of these prodrugs were determined by ¹⁹F-NMR and HPLC in vitro studies. The spacer-containing prodrug was found to be the more stable and more quickly cleaved than the other. Thereby it appeared to be a promising candidate for in vivo studies.