1. Synthesis and evaluation of indatraline-based inhibitors for trypanothione reductase.
- Author
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Walton JG, Jones DC, Kiuru P, Durie AJ, Westwood NJ, and Fairlamb AH
- Subjects
- Chromatography, High Pressure Liquid, Enzyme Inhibitors pharmacology, Magnetic Resonance Spectroscopy, Mass Spectrometry, Stereoisomerism, Enzyme Inhibitors chemical synthesis, Indans chemical synthesis, Indans pharmacology, Methylamines chemical synthesis, Methylamines pharmacology, NADH, NADPH Oxidoreductases antagonists & inhibitors
- Abstract
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., (Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
- Published
- 2011
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