Synthesis and Evaluation of 1-(1-(Benzo[b]thiophen-2-yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase

Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP (1, 1-(1-benzo[b]thiophen-2-yl-cyclohexyl) piperidine) was found to be a competitive inhibitor of...

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Detalles Bibliográficos
Autores principales: Patterson, Stephen, Jones, Deuan C, Shanks, Emma J, Frearson, Julie A, Gilbert, Ian H, Wyatt, Paul G, Fairlamb, Alan H
Formato: Texto
Lenguaje:English
Publicado: WILEY-VCH Verlag 2009
Materias:
Full Paper
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2929374/
https://www.ncbi.nlm.nih.gov/pubmed/19557802
http://dx.doi.org/10.1002/cmdc.200900098
Descripción
Sumario:Thirty two analogues of phencyclidine were synthesised and tested as inhibitors of trypanothione reductase (TryR), a potential drug target in trypanosome and leishmania parasites. The lead compound BTCP (1, 1-(1-benzo[b]thiophen-2-yl-cyclohexyl) piperidine) was found to be a competitive inhibitor of the enzyme (K(i)=1 μm) and biologically active against bloodstream T. brucei (EC(50)=10 μm), but with poor selectivity against mammalian MRC5 cells (EC(50)=29 μm). Analogues with improved enzymatic and biological activity were obtained. The structure–activity relationships of this novel series are discussed.

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