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 microM. 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.
Daunes
Sylvie
S
Department of Chemistry & Materials, The Manchester Metropolitan University, Manchester M1 5GD, United Kingdom.
D'Silva
Claudius
C
D000818:Animals; D005978:Glutathione / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D021261:Parasitic Sensitivity Tests; D013095:Spermidine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000737:chemistry / Q000494:pharmacology*; D016833:Trypanosoma brucei rhodesiense / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D014344:Trypanocidal Agents; C044809:trypanothione; D005978:Glutathione; D013095:Spermidine