Synthesis and evaluation of 1-(1-(benzo[b]thiophen-2-yl)cyclohexyl) piperidine (BTCP) analogues as inhibitors of trypanothione reductase

Abstract

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 (Ki=1 μM) and biologically active against bloodstream T. brucei (EC50=10 μM), but with poor selectivity against mammalian MRC5 cells (EC50=29 μM). Analogues with improved enzymatic and biological activity were obtained. The structure-activity relationships of this novel series are discussed. © 2009 Wiley-VCH Verlag GmbH & Co. KGaA.