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Synthesis and evaluation of indatraline-based inhibitors for trypanothione reductase.
Walton, Jeffrey G A; Jones, Deuan C; Kiuru, Paula; Durie, Alastair J; Westwood, Nicholas J; Fairlamb, Alan H.
Afiliación
  • Walton JG; School of Chemistry and Biomedical Sciences Research Complex, University of St Andrews, North Haugh, St Andrews, Fife, KY16 9ST, UK.
ChemMedChem ; 6(2): 321-8, 2011 Feb 07.
Article en En | MEDLINE | ID: mdl-21275055
The search for novel compounds of relevance to the treatment of diseases caused by trypanosomatid protozoan parasites continues. Screening of a large library of known bioactive compounds has led to several drug-like starting points for further optimisation. In this study, novel analogues of the monoamine uptake inhibitor indatraline were prepared and assessed both as inhibitors of trypanothione reductase (TryR) and against the parasite Trypanosoma brucei. Although it proved difficult to significantly increase the potency of the original compound as an inhibitor of TryR, some insight into the preferred substituent on the amine group and in the two aromatic rings of the parent indatraline was deduced. In addition, detailed mode of action studies indicated that two of the inhibitors exhibit a mixed mode of inhibition.
Asunto(s)

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores Enzimáticos / Indanos / Metilaminas / NADH NADPH Oxidorreductasas Idioma: En Revista: ChemMedChem Asunto de la revista: FARMACOLOGIA / QUIMICA Año: 2011 Tipo del documento: Article Pais de publicación: Alemania

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Inhibidores Enzimáticos / Indanos / Metilaminas / NADH NADPH Oxidorreductasas Idioma: En Revista: ChemMedChem Asunto de la revista: FARMACOLOGIA / QUIMICA Año: 2011 Tipo del documento: Article Pais de publicación: Alemania