Department of Chemistry, Chair of Organic Chemistry II, Center for Integrated Protein Science (CIPSM), Technische Universität München, Lichtenbergstrasse 4, 85747, Garching, Germany.
R&D Therapeutic Area Infectious Diseases, Sanofi-Aventis (Deutschland) GmbH, Industriepark Höchst, 65926, Frankfurt am Main, Germany.
Angew Chem Int Ed Engl. 2018 Oct 26;57(44):14440-14475. doi: 10.1002/anie.201804971. Epub 2018 Oct 11.
The public view on antibiotics as reliable medicines changed when reports about "resistant superbugs" appeared in the news. While reasons for this resistance development are easily spotted, solutions for re-establishing effective antibiotics are still in their infancy. This Review encompasses several aspects of the antibiotic development pipeline from very early strategies to mature drugs. An interdisciplinary overview is given of methods suitable for mining novel antibiotics and strategies discussed to unravel their modes of action. Select examples of antibiotics recently identified by using these platforms not only illustrate the efficiency of these measures, but also highlight promising clinical candidates with therapeutic potential. Furthermore, the concept of molecules that disarm pathogens by addressing gatekeepers of virulence will be covered. The Review concludes with an evaluation of antibacterials currently in clinical development. Overall, this Review aims to connect select innovative antimicrobial approaches to stimulate interdisciplinary partnerships between chemists from academia and industry.
当有关“耐药超级细菌”的报道出现在新闻中时，公众对抗生素作为可靠药物的看法发生了变化。虽然很容易发现这种耐药性发展的原因，但恢复有效抗生素的解决方案仍处于起步阶段。这篇综述涵盖了抗生素开发管道的几个方面，从早期策略到成熟药物。本文对适用于挖掘新型抗生素的方法和用于揭示其作用模式的策略进行了跨学科概述。最近使用这些平台鉴定的抗生素的一些例子不仅说明了这些措施的效率，而且还突出了具有治疗潜力的有前景的临床候选药物。此外，还将介绍通过解决毒力的“守门员”来消除病原体的分子的概念。这篇综述以对目前处于临床开发阶段的抗菌药物的评估结束。总的来说，这篇综述旨在将一些创新的抗菌方法联系起来，以激发学术界和工业界的化学家之间的跨学科合作。
