Saber UCV
Repositorio Institucional
Repositorio Institucional
Please use this identifier to cite or link to this item:
https://saber.ucv.ve/handle/10872/1701
|
| Title: | Aziridine-2,3-Dicarboxylates, Peptidomimetic Cysteine Protease Inhibitors with Antileishmanial Activity |
| Authors: | Ponte-Sucre, Alicia Vicik, Radim Schultheis, Martina Schirmeister, Tanja Moll, Heidrun |
| Keywords: | Aziridine-2,3-Dicarboxylates Cysteine Protease Inhibitors Leishmania |
| Issue Date: | 23-Aug-2012 |
| Series/Report no.: | Antimicrobial Agents and Chemotherapy;50: 2439-2447, 2006 |
| Abstract: | serious side effects, and there is a worldwide increasing frequency of chemoresistance to antimonials. These issues emphasize the urgent need for affordable alternative drugs against leishmaniasis. Leishmania cysteine proteases are essential for parasite growth, differentiation, pathogenicity, and virulence and are thus attractive targets for combating leishmaniasis. Herein we demonstrate that the cysteine protease inhibitors aziridine- 2,3-dicarboxylates 13b and 13e impaired promastigote growth at mid-micromolar concentrations and decreased the infection rate of peritoneal macrophages at concentrations 8- to 13-fold lower than those needed to inhibit parasite replication. Simultaneous treatment of infected cells with compound 13b and gamma interferon resulted in an even further reduction of the concentration needed for a significant decrease in macrophage infection rate. Notably, treatment with the compounds alone modulated the cytokine secretion of infected macrophages, with increased levels of interleukin-12 and tumor necrosis factor alpha. Furthermore, the decreased infection rate in the presence of compound 13b correlated with increased nitric oxide production by macrophages. Importantly, at the concentrations used herein, compounds 13b and 13e were not toxic against fibroblasts, macrophages, or dendritic cells. Together, these results suggest that the aziridine-2,3-dicarboxylates 13b and 13e are potential antileishmanial lead compounds with low toxicity against host cells and selective antiparasitic effects. |
| URI: | http://hdl.handle.net/10872/1701 |
| ISSN: | 1098-6596 |
| Appears in Collections: | Artículos Publicados |
Files in This Item:
|
Items in DSpace are protected by copyright, with all rights reserved, unless otherwise indicated.