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Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors
Authors:Dr. Gordon J. Florence  Andrew L. Fraser  Dr. Eoin R. Gould  Elizabeth F. King  Stefanie K. Menzies  Dr. Joanne C. Morris  Marie I. Thomson  Dr. Lindsay B. Tulloch  Marija K. Zacharova  Prof. Dr. Terry K. Smith
Affiliation:EaStCHEM School of Chemistry and School of Biology, Biomedical Sciences Research Complex, University of St.?Andrews, North Haugh, St.?Andrews, UK
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.
Keywords:[3+2] cycloaddition  drug discovery  natural product analogues  trypanosomatids
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