Design, synthesis, and evaluation of potential prodrugs of DFMO for reductive activation

A series of potential DFMO prodrugs was designed through the incorporation of 4-nitrobenzyl ester or carbamate groups for potential activation by trypanosomal nitroreductase. It was found that only modification of Nε-amino group of DFMO by 4-nitro-2-fluorobenzyloxycarbonyl resulted in significant trypanocidal activity and could serve as a lead for further investigation.