N-Benzyloxycarbonyl-S-(2,4-dinitrophenyl)glutathione dibutyl diester is inhibitory to melarsoprol resistant cell lines overexpressing the T. bruceiMRPA transporter |
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Authors: | Vincent P. Alibu Sylvie Daunes Claudius D’Silva |
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Affiliation: | 1. ZMBH, Universitat Heidelberg, Im Neuenheimer Feld 282, 69120 Heidelberg, Germany;2. School of Chemistry & Environmental Sciences, The Manchester Metropolitan University, Faculty of Science and Engineering, John Dalton Building, Chester Street, Manchester M1 5GD, UK |
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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. |
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Keywords: | Glutathione Trypanosomiasis MRPA Melarsoprol |
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