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Eur J Med Chem ; 62: 466-77, 2013 Apr.
Article de Anglais | MEDLINE | ID: mdl-23395967

RÉSUMÉ

The activity of a family scorpiand-like azamacrocycles against Leishmania infantum and Leishmania braziliensis was studied using promastigotes, axenic and intracellular amastigotes forms. All the compounds are more active and less toxic than meglumine antimoniate (Glucantime). Moreover, the data on infection rates and amastigotes showed that compounds P2Py, PN and P3Py are the most active against both species of Leishmania. On the other hand, studies on the inhibitory effect of these compounds on SOD enzymes showed that while the inhibition of the Fe-SOD enzyme of the promastigote forms of the parasites is remarkable, the inhibition of human CuZn-SOD and Mn-SOD from Escherichia coli is negligible. The ultrastructural alterations observed in treated promastigote forms confirmed that the compounds having the highest activity were those causing the largest cell damage. The modifications observed by (1)H NMR, and the amounts of catabolites excreted by the parasites after treatment with the compounds, suggested that the catabolic mechanism could depend on the structure of the side chains linked to the aza-scorpiand macrocycles.


Sujet(s)
Antiprotozoaires/pharmacologie , Composés aza/pharmacologie , Leishmania brasiliensis/effets des médicaments et des substances chimiques , Leishmania infantum/effets des médicaments et des substances chimiques , Composés macrocycliques/pharmacologie , Antiprotozoaires/synthèse chimique , Antiprotozoaires/composition chimique , Composés aza/synthèse chimique , Composés aza/composition chimique , Relation dose-effet des médicaments , Composés macrocycliques/synthèse chimique , Composés macrocycliques/composition chimique , Structure moléculaire , Tests de sensibilité parasitaire , Relation structure-activité
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