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, and 3 and its derivatives, showed reduced inhibitory activity against T. bruceiMRPA, indicating them to be substrates and susceptible to resistance.
Alibu, V.P.; Daunes, S.; D’Silva, C. N-Benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione dibutyl diester is inhibitory to melarsoprol resistant cell lines overexpressing the iT. bruceiiMRPA transporter. Bioorganic and Medicinal Chemistry Letters (2013) 23 (15) 1351-4353.
N-Benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione dibutyl diester is inhibitory to melarsoprol resistant cell lines overexpressing the <i>T. brucei</i>MRPA transporter