Synthesis and Evaluation of 1‐(1‐(Benzo[b]thiophen‐2‐yl)cyclohexyl)piperidine (BTCP) Analogues as Inhibitors of Trypanothione Reductase |
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| Authors: | Stephen Patterson Dr Deuan?C Jones Dr Emma?J Shanks Dr Julie?A Frearson Prof Ian?H Gilbert Prof Paul?G Wyatt Prof Alan?H Fairlamb Prof |
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| Affiliation: | Division of Biological Chemistry & Drug Discovery, College of Life Sciences, University of Dundee, Dundee, DD1 5EH (UK), Fax: (+44)?1382?385542 |
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| 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‐benzob]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. |
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| Keywords: | BTCP inhibitors medicinal chemistry trypanosoma brucei trypanothione reductase |
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