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

ABSTRACT: 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.

SUBMITTER: Florence GJ

PROVIDER: S-EPMC5111590 | biostudies-literature | 2016 Jul

REPOSITORIES: biostudies-literature

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

Florence Gordon J GJ Fraser Andrew L AL Gould Eoin R ER King Elizabeth F EF Menzies Stefanie K SK Morris Joanne C JC Thomson Marie I MI Tulloch Lindsay B LB Zacharova Marija K MK Smith Terry K TK

ChemMedChem 20160610 14

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 ...[more]

PMID: 27283448

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