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Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors

Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the...

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Autores principales: Florence, Gordon J., Fraser, Andrew L., Gould, Eoin R., King, Elizabeth F., Menzies, Stefanie K., Morris, Joanne C., Thomson, Marie I., Tulloch, Lindsay B., Zacharova, Marija K., Smith, Terry K.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111590/
https://www.ncbi.nlm.nih.gov/pubmed/27283448
http://dx.doi.org/10.1002/cmdc.201600210
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author Florence, Gordon J.
Fraser, Andrew L.
Gould, Eoin R.
King, Elizabeth F.
Menzies, Stefanie K.
Morris, Joanne C.
Thomson, Marie I.
Tulloch, Lindsay B.
Zacharova, Marija K.
Smith, Terry K.
author_facet Florence, Gordon J.
Fraser, Andrew L.
Gould, Eoin R.
King, Elizabeth F.
Menzies, Stefanie K.
Morris, Joanne C.
Thomson, Marie I.
Tulloch, Lindsay B.
Zacharova, Marija K.
Smith, Terry K.
author_sort Florence, Gordon J.
collection PubMed
description Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin‐inspired derivatives, namely 3,5‐isoxazoles, furoxans, and furazans. Several of these compounds maintain low‐micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment.
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spelling pubmed-51115902016-11-16 Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors Florence, Gordon J. Fraser, Andrew L. Gould, Eoin R. King, Elizabeth F. Menzies, Stefanie K. Morris, Joanne C. Thomson, Marie I. Tulloch, Lindsay B. Zacharova, Marija K. Smith, Terry K. ChemMedChem Communications Neglected tropical diseases caused by parasitic infections are an ongoing and increasing concern. They are a burden to human and animal health, having the most devastating effect on the world′s poorest countries. Building upon our previously reported triazole analogues, in this study we describe the synthesis and biological testing of other novel heterocyclic acetogenin‐inspired derivatives, namely 3,5‐isoxazoles, furoxans, and furazans. Several of these compounds maintain low‐micromolar levels of inhibition against Trypanosoma brucei, whilst having no observable inhibitory effect on mammalian cells, leading to the possibility of novel lead compounds for selective treatment. John Wiley and Sons Inc. 2016-06-10 2016-07-19 /pmc/articles/PMC5111590/ /pubmed/27283448 http://dx.doi.org/10.1002/cmdc.201600210 Text en © 2016 The Authors. Published by Wiley-VCH Verlag GmbH & Co. KGaA. This is an open access article under the terms of the Creative Commons Attribution (http://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Communications
Florence, Gordon J.
Fraser, Andrew L.
Gould, Eoin R.
King, Elizabeth F.
Menzies, Stefanie K.
Morris, Joanne C.
Thomson, Marie I.
Tulloch, Lindsay B.
Zacharova, Marija K.
Smith, Terry K.
Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
title Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
title_full Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
title_fullStr Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
title_full_unstemmed Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
title_short Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
title_sort development of simplified heterocyclic acetogenin analogues as potent and selective trypanosoma brucei inhibitors
topic Communications
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5111590/
https://www.ncbi.nlm.nih.gov/pubmed/27283448
http://dx.doi.org/10.1002/cmdc.201600210
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