In vitro evaluation of a series of N-, S-, and COOH-blocked glutathione derivatives have been carried out by D'Silva and Daunes [81] against bloodstream form Trypanosoma brucei trypomastigotes, to identify the determinants necessary for activity and for further development into an active lead structure. The results shows that N, S-blocked glutathione diesters are the most active inhibitors of T. brucei parasites and that N-acetyl-S-benzyloxycarbonylglutathione dimethyl ester (compound 5) and the N,S-benzyloxycarbonyl-S-2,4dinitrophenylglutathione diester derivatives (compounds 17-19 & 21) (Figure 30 ) represent lead structures possessing minimal toxicity which potentially could be developed further to yield a therapeutically active agent for the treatment of trypanosomiasis.