Imidazolium compounds are active against all stages of Trypanosoma cruzi.
Identifieur interne : 002883 ( Main/Exploration ); précédent : 002882; suivant : 002884Imidazolium compounds are active against all stages of Trypanosoma cruzi.
Auteurs : Paula Faral-Tello [Uruguay] ; Mary Liang [États-Unis] ; Graciela Mahler [Uruguay] ; Peter Wipf [États-Unis] ; Carlos Robello [Uruguay]Source :
- International journal of antimicrobial agents [ 1872-7913 ] ; 2014.
Descripteurs français
- KwdFr :
- Animaux, Antiprotozoaires (pharmacologie), Imidazoles (), Imidazoles (pharmacologie), Microscopie électronique à transmission, Mitochondries (), Mitochondries (ultrastructure), Nitroimidazoles (), Nitroimidazoles (pharmacologie), Relation structure-activité, Trypanosoma cruzi (), Trypanosoma cruzi (ultrastructure).
- MESH :
English descriptors
- KwdEn :
- Animals, Antiprotozoal Agents (pharmacology), Imidazoles (chemistry), Imidazoles (pharmacology), Microscopy, Electron, Transmission, Mitochondria (drug effects), Mitochondria (ultrastructure), Nitroimidazoles (chemistry), Nitroimidazoles (pharmacology), Structure-Activity Relationship, Trypanosoma cruzi (drug effects), Trypanosoma cruzi (ultrastructure).
- MESH :
- chemical , chemistry : Imidazoles, Nitroimidazoles.
- chemical , pharmacology : Antiprotozoal Agents, Imidazoles, Nitroimidazoles.
- drug effects : Mitochondria, Trypanosoma cruzi.
- ultrastructure : Mitochondria, Trypanosoma cruzi.
- Animals, Microscopy, Electron, Transmission, Structure-Activity Relationship.
Abstract
Imidazolium salts are best known for their applications in organic synthesis as room-temperature ionic liquids, or as precursors of stable carbenes, but they also show important biological properties such as anti-oxidative effects, induction of mitochondrial membrane permeabilisation and inhibition of the infection cycle of Plasmodium falciparum. For these reasons, and since chemotherapy for Chagas disease is inefficient, the aim of this study was to test the use of imidazolium compounds against the kinetoplastid haemoflagellate aetiological agent for this disease, namely Trypanosoma cruzi. The results show that five of the tested compounds are more effective than the reference drug benznidazole against the epimastigote and trypomastigote forms of T. cruzi. Moreover, intracellular amastigotes were also affected by the compounds, which showed lower toxicity in host cells. Transmission electron microscopy analysis demonstrated that the tested agents induced alterations of the kinetoplast and particularly of the mitochondria, leading to extraordinary swelling of the organelle. These results further demonstrate that the test agents with the best profile are those bearing symmetrical bulky substituents at N(1) and N(3), displaying promising activity against all forms of T. cruzi, interesting selectivity indexes and exceptional activity at low doses. Accordingly, these agents represent promising candidates for the treatment of Chagas disease.
DOI: 10.1016/j.ijantimicag.2013.10.019
PubMed: 24359836
Affiliations:
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Le document en format XML
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For these reasons, and since chemotherapy for Chagas disease is inefficient, the aim of this study was to test the use of imidazolium compounds against the kinetoplastid haemoflagellate aetiological agent for this disease, namely Trypanosoma cruzi. The results show that five of the tested compounds are more effective than the reference drug benznidazole against the epimastigote and trypomastigote forms of T. cruzi. Moreover, intracellular amastigotes were also affected by the compounds, which showed lower toxicity in host cells. Transmission electron microscopy analysis demonstrated that the tested agents induced alterations of the kinetoplast and particularly of the mitochondria, leading to extraordinary swelling of the organelle. These results further demonstrate that the test agents with the best profile are those bearing symmetrical bulky substituents at N(1) and N(3), displaying promising activity against all forms of T. cruzi, interesting selectivity indexes and exceptional activity at low doses. Accordingly, these agents represent promising candidates for the treatment of Chagas disease.</div></front></TEI><affiliations><list><country><li>Uruguay</li><li>États-Unis</li></country><region><li>Pennsylvanie</li></region><settlement><li>Pittsburgh</li></settlement><orgName><li>Université de Pittsburgh</li></orgName></list><tree><country name="Uruguay"><noRegion><name sortKey="Faral Tello, Paula" sort="Faral Tello, Paula" uniqKey="Faral Tello P" first="Paula" last="Faral-Tello">Paula Faral-Tello</name></noRegion><name sortKey="Mahler, Graciela" sort="Mahler, Graciela" uniqKey="Mahler G" first="Graciela" last="Mahler">Graciela Mahler</name><name sortKey="Robello, Carlos" sort="Robello, Carlos" uniqKey="Robello C" first="Carlos" last="Robello">Carlos Robello</name></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Liang, Mary" sort="Liang, Mary" uniqKey="Liang M" first="Mary" last="Liang">Mary Liang</name></region><name sortKey="Wipf, Peter" sort="Wipf, Peter" uniqKey="Wipf P" first="Peter" last="Wipf">Peter Wipf</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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