A novel enediyne prodrug for antibody-directed enzyme prodrug therapy (ADEPT) using E. coli B nitroreductase

The synthesis of a novel enediyne 2, and its cytotoxicity and activation by the nitroreductase enzyme NR2 from Esherichia coli B, are described. In contrast to closely related analogues, 2 exhibits a 90-fold increase in cytotoxicity against UV4 cells in the presence of the enzyme and NADH, suggesting its potential as a prodrug for Antibody-Directed Enzyme Prodrug Therapy in conjunction with E. coli nitroreductase.