title: N-Benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione dibutyl diester is inhibitory to melarsoprol resistant cell lines overexpressing the T. bruceiMRPA transporter.
abstract: A series of glutathione derivatives 1-4, modified at the N,S and/or COOH sites, with in vitro antitrypanosomal activity were tested against bloodstream form Trypanosoma brucei 247 wild type and a T. b. brucei 247 strain over-expressing the multiple drug resistance protein (MRPA) by 50-100x to assess the susceptibility of these compounds to resistance by the TbMRP protein. Of the compounds tested, only compound 1 inhibited both bloodstream form T. brucei and T. bruceiMRPA, with a resistance factor of 1.4, indicating it to be an inhibitor of this protein and proteins acting in synergy with the transporter, whilst 2 &3 and its derivatives showed reduced inhibitory activity against T. bruceiMRPA, indicating them to be substrates and susceptible to resistance.
authors.affiliation: ZMBH, Universitat Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany.
authors.forename: Vincent P
authors.initials: VP
authors.lastname: Alibu
authors.forename: Sylvie
authors.initials: S
authors.lastname: Daunes
authors.forename: Claudius
authors.initials: C
authors.lastname: D'Silva
mesh_terms: D005978:Glutathione / Q000737:chemistry* / Q000378:metabolism; D026901:Membrane Transport Proteins / Q000378:metabolism; D011485:Protein Binding; D015800:Protozoan Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D021281:Quantitative Structure-Activity Relationship; D014346:Trypanosoma brucei brucei / Q000378:metabolism*
chemical_list: C461386:MRPA protein, Trypanosoma brucei; D026901:Membrane Transport Proteins; C585782:N-benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione dibutyl diester; D015800:Protozoan Proteins; D005978:Glutathione