Development of simplified heterocyclic acetogenin analogues as potent and selective Trypanosoma brucei inhibitors

Gordon J. Florence; Andrew L. Fraser; Eoin R. Gould; Elizabeth F. King; Stefanie K. Menzies; Joanne C. Morris; Marie I. Thomson; Lindsay B. Tulloch; Marija K. Zacharova; Terry K. Smith

doi:10.1002/cmdc.201600210

Development of simplified heterocyclic acetogenin analogues as potent and selective Trypanosoma brucei inhibitors

Gordon J. Florence, Andrew L. Fraser, Eoin R. Gould, Elizabeth F. King, Stefanie K. Menzies, Joanne C. Morris, Marie I. Thomson, Lindsay B. Tulloch, Marija K. Zacharova, Terry K. Smith

Research output: Contribution to journal › Letter › peer-review

Abstract

Neglected tropical diseases caused by parasitic infections are an on-going and increasing concern and 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.

Original language	English
Pages (from-to)	1503-1506
Number of pages	4
Journal	ChemMedChem
Volume	11
Issue number	14
Early online date	10 Jun 2016
DOIs	https://doi.org/10.1002/cmdc.201600210
Publication status	Published - 19 Jul 2016

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

[3+2] cycloaddition
Drug discovery
Natural product analogues
Trypanosomatids

Access to Document

10.1002/cmdc.201600210

cmdc201600210-revised-PURE
© 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim. This work is made available online in accordance with the publisher’s policies. This is the author created, accepted version manuscript following peer review and may differ slightly from the final published version. The final published version of this work is available at https://dx.doi.org/10.1002/cmdc.201600210
Accepted author manuscript, 365 KBLicence: Unspecified

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@article{6a1ae42a9a934f5ebdd59144a9a82588,

title = "Development of simplified heterocyclic acetogenin analogues as potent and selective Trypanosoma brucei inhibitors",

abstract = "Neglected tropical diseases caused by parasitic infections are an on-going and increasing concern and burden to human and animal health, having the most devastating effect on the world{\textquoteright}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.",

keywords = "[3+2] cycloaddition, Drug discovery, Natural product analogues, Trypanosomatids",

author = "Florence, \{Gordon J.\} and Fraser, \{Andrew L.\} and Gould, \{Eoin R.\} and King, \{Elizabeth F.\} and Menzies, \{Stefanie K.\} and Morris, \{Joanne C.\} and Thomson, \{Marie I.\} and Tulloch, \{Lindsay B.\} and Zacharova, \{Marija K.\} and Smith, \{Terry K.\}",

note = "This work was funded by the Leverhulme Trust (GJF), and the Wellcome Trust (TKS, WT 093228).",

year = "2016",

month = jul,

day = "19",

doi = "10.1002/cmdc.201600210",

language = "English",

volume = "11",

pages = "1503--1506",

journal = "ChemMedChem",

issn = "1860-7179",

publisher = "John Wiley \& Sons, Ltd",

number = "14",

}

TY - JOUR

T1 - Development of simplified heterocyclic acetogenin analogues as potent and selective Trypanosoma brucei inhibitors

AU - Florence, Gordon J.

AU - Fraser, Andrew L.

AU - Gould, Eoin R.

AU - King, Elizabeth F.

AU - Menzies, Stefanie K.

AU - Morris, Joanne C.

AU - Thomson, Marie I.

AU - Tulloch, Lindsay B.

AU - Zacharova, Marija K.

AU - Smith, Terry K.

N1 - This work was funded by the Leverhulme Trust (GJF), and the Wellcome Trust (TKS, WT 093228).

PY - 2016/7/19

Y1 - 2016/7/19

N2 - Neglected tropical diseases caused by parasitic infections are an on-going and increasing concern and 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.

AB - Neglected tropical diseases caused by parasitic infections are an on-going and increasing concern and 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.

KW - [3+2] cycloaddition

KW - Drug discovery

KW - Natural product analogues

KW - Trypanosomatids

UR - https://www.scopus.com/pages/publications/84978763282

U2 - 10.1002/cmdc.201600210

DO - 10.1002/cmdc.201600210

M3 - Letter

SN - 1860-7179

VL - 11

SP - 1503

EP - 1506

JO - ChemMedChem

JF - ChemMedChem

IS - 14

ER -

Development of simplified heterocyclic acetogenin analogues as potent and selective Trypanosoma brucei inhibitors

Abstract

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Keywords

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Natural Product Drug Discovery: Natural Product Drug Discovery: Design and Development of Novel Tryoanosoma brucei Inhibitors

Investigating Trypanosoma brucei's: Investigating Trypanosoma Brucei's Unusual Inositol Metabolism

Gordon Florence

Data underpinning- Development of simplified heterocyclic acetogenin analogues as potent and selective Trypanosoma brucei inhibitors

Simplifying nature: towards the design of broad spectrum kinetoplastid inhibitors, inspired by acetogenins

Cite this

Development of simplified heterocyclic acetogenin analogues as potent and selective Trypanosoma brucei inhibitors

Abstract

UN SDGs

Keywords

Access to Document

Handle.net

Other files and links

Fingerprint

Projects

Natural Product Drug Discovery: Natural Product Drug Discovery: Design and Development of Novel Tryoanosoma brucei Inhibitors

Investigating Trypanosoma brucei's: Investigating Trypanosoma Brucei's Unusual Inositol Metabolism

Profiles

Gordon Florence

Datasets

Data underpinning- Development of simplified heterocyclic acetogenin analogues as potent and selective Trypanosoma brucei inhibitors

Research output

Simplifying nature: towards the design of broad spectrum kinetoplastid inhibitors, inspired by acetogenins

Cite this