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作为克服抗生素耐药性平台的天然产物

Natural Products as Platforms To Overcome Antibiotic Resistance.

作者信息

Rossiter Sean E, Fletcher Madison H, Wuest William M

机构信息

Department of Chemistry, Emory University , 1515 Dickey Drive, Atlanta, Georgia 30322, United States.

Department of Chemistry, Temple University , 1901 North 13th Street, Philadelphia, Pennsylvania 19122, United States.

出版信息

Chem Rev. 2017 Oct 11;117(19):12415-12474. doi: 10.1021/acs.chemrev.7b00283. Epub 2017 Sep 27.

Abstract

Natural products have served as powerful therapeutics against pathogenic bacteria since the golden age of antibiotics of the mid-20th century. However, the increasing frequency of antibiotic-resistant infections clearly demonstrates that new antibiotics are critical for modern medicine. Because combinatorial approaches have not yielded effective drugs, we propose that the development of new antibiotics around proven natural scaffolds is the best short-term solution to the rising crisis of antibiotic resistance. We analyze herein synthetic approaches aiming to reengineer natural products into potent antibiotics. Furthermore, we discuss approaches in modulating quorum sensing and biofilm formation as a nonlethal method, as well as narrow-spectrum pathogen-specific antibiotics, which are of interest given new insights into the implications of disrupting the microbiome.

摘要

自20世纪中叶抗生素的黄金时代以来,天然产物一直是对抗病原菌的有力治疗药物。然而,抗生素耐药性感染的频率不断增加,清楚地表明新抗生素对现代医学至关重要。由于组合方法尚未产生有效的药物,我们提出围绕经过验证的天然骨架开发新抗生素是应对抗生素耐药性不断上升危机的最佳短期解决方案。我们在此分析旨在将天然产物重新设计成强效抗生素的合成方法。此外,我们讨论了作为一种非致命方法调节群体感应和生物膜形成的方法,以及窄谱病原体特异性抗生素,鉴于对破坏微生物群影响的新见解,这些抗生素备受关注。

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Natural Products as Platforms To Overcome Antibiotic Resistance.作为克服抗生素耐药性平台的天然产物
Chem Rev. 2017 Oct 11;117(19):12415-12474. doi: 10.1021/acs.chemrev.7b00283. Epub 2017 Sep 27.

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