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作为强效且选择性布氏锥虫抑制剂的简化杂环乙酰原素类似物的研发。

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

作者信息

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

机构信息

EaStCHEM School of Chemistry and School of Biology, Biomedical Sciences Research Complex, University of St. Andrews, North Haugh, St. Andrews, KY16 9ST, UK.

出版信息

ChemMedChem. 2016 Jul 19;11(14):1503-6. doi: 10.1002/cmdc.201600210. Epub 2016 Jun 10.

DOI:10.1002/cmdc.201600210
PMID:27283448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5111590/
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.

摘要

由寄生虫感染引起的被忽视热带病一直是且日益令人担忧。它们对人类和动物健康构成负担,对世界上最贫穷国家产生了最具破坏性的影响。基于我们之前报道的三唑类似物,在本研究中,我们描述了其他新型杂环类源自产乙酸素的衍生物的合成及生物学测试,即3,5-异恶唑、呋咱和呋咱烷。这些化合物中有几种对布氏锥虫保持低微摩尔水平的抑制作用,同时对哺乳动物细胞没有可观察到的抑制作用,从而有产生用于选择性治疗的新型先导化合物的可能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a7/5111590/d5a98bf324ec/CMDC-11-1503-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a7/5111590/9711c1ddd52f/CMDC-11-1503-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a7/5111590/bd393bf9421d/CMDC-11-1503-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a7/5111590/59f9d81bc5c3/CMDC-11-1503-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a7/5111590/d5a98bf324ec/CMDC-11-1503-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a7/5111590/9711c1ddd52f/CMDC-11-1503-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a7/5111590/bd393bf9421d/CMDC-11-1503-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a7/5111590/59f9d81bc5c3/CMDC-11-1503-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/76a7/5111590/d5a98bf324ec/CMDC-11-1503-g004.jpg

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