Glutathione Derivatives Active against Trypanosoma brucei rhodesiense and T. brucei brucei In Vitro

Diesters based on N-benzyloxycarbonyl-S-(2,4-dinitrophenyl) GSH (CBzGSDNP) containing linear alcohols 3 to 9, branched alcohols 10 to 20, or heteroatom linear alcohols 21 to 25, were investigated as in vitro inhibitors of pathogenic parasites. Diesters 3 to 25 were better inhibitors of Trypanosoma brucei rhodesiense than of T. brucei brucei and had low cytotoxicities. The most active compound had a 50% effective dose (ED(50)) of 0.2 μM. A quantitative structure activity regression equation relating the log (1/ED(50)) versus the hydrophobicity parameter (log P), Taft's steric parameter (E(s)), molecular weight (MW), and the WienI descriptor (W) was determined, and the species difference was found to be related to membrane penetration and steric effects.