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 the enzyme (K-i = 1 mu m) and biologically active against bloodstream T brucei (EC50 = 10 mu m), but with poor selectivity against mammalian MRC5 cells (EC50 = 29 mu m). Analogues with improved enzymatic and biological activity were obtained. The structure-activity relationships of this novel series are discussed.