Publicación:
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors
The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors
No hay miniatura disponible
Fecha
2008
Autores
Galarreta B.C.
Sifuentes R.
Carrillo A.K.
Sanchez L.
Amado M.d.R.I.
Maruenda H.
Título de la revista
Revista ISSN
Título del volumen
Editor
Elsevier Ltd
Proyectos de investigación
Unidades organizativas
Número de la revista
Abstracto
Twenty-three heterocyclic compounds were evaluated for their potential as trypanothione reductase
inhibitors. As a result, the harmaline, 10-thiaisoalloxazine, and aspidospermine frameworks were identified as the basis of inhibitors of Trypanosoma cruzi trypanothione reductase. Two new compounds
showed moderately strong, linear competitive inhibition, namely N,N-dimethyl-N-[3-(7-methoxy-1-
methyl-3,4-dihydro-9H-b-carbolin-9-yl)propyl]amine (15) and 1,3-bis[3-(dimethylamino)propyl]-1,5-
dihydro-2H-pyrimido[4,5-b][1,4]benzothiazine-2,4(3H)-dione (21), with Ki values of 35.1 ± 3.5 lM and
26.9 ±1.9 lM, respectively. Aspidospermine (25) inhibited T. cruzi TryR with a Ki of 64.6 ± 6.2 lM. None
of the compounds inhibited glutathione reductase. Their toxicity toward promastigotes of Leishmania
amazonensis was assessed.
Descripción
Financial support was received from The Wellcome Trust Travel Awards 2000, 2002; TWAS 02-051; CONCYTEC: 2002-2003, 441-2004 and PUCP-DAI: 3054, 0198, 3414, and E-032.
Palabras clave
Trypanosomatid,
Trypanothione reductase,
Enzymatic inhibition