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

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. (2016) Development of Simplified Heterocyclic Acetogenin Analogues as Potent and Selective Trypanosoma brucei Inhibitors. ChemMedChem, 11 (14). pp. 1503-1506. ISSN 1860-7179

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.