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 - The work was funded by the Leverhulme Trust (G.J.F.), and the Wellcome Trust (T.K.S., WT093228). We thank the EPSRC National Mass Spectrometry Service Centre, Swansea, UK for mass spectrometry services.
PY - 2016/7/19
Y1 - 2016/7/19
N2 - 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.
AB - 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.
KW - Acetogenins/chemical synthesis
KW - Cycloaddition Reaction
KW - HeLa Cells
KW - Humans
KW - Isoxazoles/chemical synthesis
KW - Oxadiazoles/chemical synthesis
KW - Oximes/chemical synthesis
KW - Trypanocidal Agents/chemical synthesis
KW - Trypanosoma brucei brucei/drug effects
U2 - 10.1002/cmdc.201600210
DO - 10.1002/cmdc.201600210
M3 - Article
C2 - 27283448
SN - 1860-7179
VL - 11
SP - 1503
EP - 1506
JO - ChemMedChem
JF - ChemMedChem
IS - 14
ER -
