Fournet Alain, Inchausti A., Yaluff G., Rojas de Arias A., GuinaudeauH., Bruneton J., Breidenbach M.A., Karplus P.A., Faerman C.H. (1998). Trypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase. Journal of Enzyme Inhibition, 13, p. 1-9.
Titre du document
Trypanocidal bisbenzylisoquinoline alkaloids are inhibitors of trypanothione reductase
Année de publication
1998
Type de document
Article
Auteurs
Fournet Alain, Inchausti A., Yaluff G., Rojas de Arias A., GuinaudeauH., Bruneton J., Breidenbach M.A., Karplus P.A., Faerman C.H.
Source
Journal of Enzyme Inhibition, 1998,
13, p. 1-9
Eleven bisbenzylisoquinoline (BBIQ) alkaloids were studied for in vitro trypanocidal activity against trypomastigote forms of the Y strain of Trypanosoma cruzi. The inhibitory activity of these compounds against trypanothione reductase (TR), a target enzyme for chemotherapy against Chagas disease, was also studied. Six BBIQ alkaloids (antioquine, cepharanthine, daphnoline, limacine, cycleanine and (-) curine) displayed a 50% lethal concentration (LC50) against T. cruzi of less than 100 microM. Daphnoline and curine, with LC50 values of 10 microM, are attractive for further investigation as potential anti-Chagasic drugs. Kinetic analyses suggested the BBIQ alkaloids are mixed inhibitors of TR. These compounds are reasonably potent inhibitors of TR ; the best TR inhibitor, cepharanthine, had an IC50 of 15 microM, which is the same order of magnitude as its LC50 against T. cruzi. The similar magnitudes of the IC50 and LC50 values suggest that inhibition of TR could contribute to the trypanocidal activity exhibited by the BBIQ alkaloids. (Résumé d'auteur)
Plan de classement
Lutte [052GLOTRY03]
Descripteurs
MALADIE DE CHAGAS ; TRAITEMENT MEDICAL ; ALCALOIDE ; INHIBITEUR DE LA TRYPANOTHIONE REDUCTASE ; ALCALOIDE TRYPANOCIDE ; BISBENZYLISOQUINOLEINE
