Cell permeation of a Trypanosoma brucei aldolase inhibitor: Evaluation of different enzyme-labile phosphate protecting groups

A series of four prodrugs directed against Trypanosoma brucei aldolase bearing various transient enzyme-labile phosphate protecting groups was developed. Herein, we describe the synthesis and evaluation of cell permeation of these prodrugs. The oxymethyl derivative was the most efficient prodrug with a good recovering of the free drug (IC50 = 20 μM) and without any measurable cytotoxicity.