The use of natural product scaffolds as leads in the search for trypanothione reductase inhibitors

Betty C. Galarreta, Roxana Sifuentes, Angela K. Carrillo, Luis Sanchez, Maria del Rosario I. Amado, Helena Maruenda

Producción científica: Contribución a una revistaArtículorevisión exhaustiva

28 Citas (Scopus)

Resumen

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-β-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 μM and 26.9 ± 1.9 μM, respectively. Aspidospermine (25) inhibited T. cruzi TryR with a Ki of 64.6 ± 6.2 μM. None of the compounds inhibited glutathione reductase. Their toxicity toward promastigotes of Leishmania amazonensis was assessed.

Idioma originalInglés
Páginas (desde-hasta)6689-6695
Número de páginas7
PublicaciónBioorganic and Medicinal Chemistry
Volumen16
N.º14
DOI
EstadoPublicada - 15 jul. 2008

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