Saber UCV
Repositorio Institucional
Repositorio Institucional
Please use this identifier to cite or link to this item:
https://saber.ucv.ve/handle/10872/1703
|
| Title: | Aziridine-2,3-dicarboxylate inhibitors targeting the major cysteine protease of Trypanosoma brucei as lead trypanocidal agents |
| Authors: | Vicik, Radim Hoerr, Verena Glaser, Melanie Schultheis, Martina Hansell, Elizabeth McKerrow, James H. Holzgrabe, Ulrike Caffrey, Conor R. Ponte-Sucre, Alicia Moll, Heidrun Stich, August Schirmeister, Tanja |
| Keywords: | Aziridine-2,3-dicarboxylate inhibitors cysteine protease Trypanosoma brucei |
| Issue Date: | 23-Aug-2012 |
| Series/Report no.: | Bioorganic Medicinal Chemistry Letters;16:2753-2757, 2006. |
| Abstract: | The protozoan parasite Trypanosoma brucei causes Human African trypanosomiasis, which is fatal if left untreated. Due to the toxicity of currently used drugs and emerging drug resistance, there is an urgent need for novel therapies. The major trypanosome papain-like cysteine protease expressed by the parasite (e.g., rhodesain in T. b. rhodesiense) is considered an important target for the development of new trypanocidal drugs. Series of aziridine-2,3-dicarboxylate-based cysteine protease inhibitors have been tested, most of them inhibiting rhodesain in the low micromolar range. Among these, only dibenzyl aziridine-2,3-dicarboxylates display trypanocidal activity being equipotent to the drug eflornithine. The Leu-Pro-containing aziridinyl tripeptides 13a–f are the most promising as they are not cytotoxic to macrophages up to concentrations of 125 mcM. |
| URI: | http://hdl.handle.net/10872/1703 |
| ISSN: | 0968-0896 |
| Appears in Collections: | Artículos Publicados |
Files in This Item:
|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.