New Structural Templates for Clinically Validated and Novel Targets in Antimicrobial Drug Research and Development

Part of the Current Topics in Microbiology and Immunology book series (CT MICROBIOLOGY, volume 398)


The development of bacterial resistance against current antibiotic drugs necessitates a continuous renewal of the arsenal of efficacious drugs. This imperative has not been met by the output of antibiotic research and development of the past decades for various reasons, including the declining efforts of large pharma companies in this area. Moreover, the majority of novel antibiotics are chemical derivatives of existing structures that represent mostly step innovations, implying that the available chemical space may be exhausted. This review negates this impression by showcasing recent achievements in lead finding and optimization of antibiotics that have novel or unexplored chemical structures. Not surprisingly, many of the novel structural templates like teixobactins, lysocin, griselimycin, or the albicidin/cystobactamid pair were discovered from natural sources. Additional compounds were obtained from the screening of synthetic libraries and chemical synthesis, including the gyrase-inhibiting NTBI’s and spiropyrimidinetrione, the tarocin and targocil inhibitors of wall teichoic acid synthesis, or the boronates and diazabicyclo[3.2.1]octane as novel β-lactamase inhibitors. A motif that is common to most clinically validated antibiotics is that they address hotspots in complex biosynthetic machineries, whose functioning is essential for the bacterial cell. Therefore, an introduction to the biological targets—cell wall synthesis, topoisomerases, the DNA sliding clamp, and membrane-bound electron transport—is given for each of the leads presented here.


Wall Teichoic Acid ADMET Property Antibacterial Target Antibiotic Research Division Septum 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



We thank Dr. Dr. Werner Tegge, Giambattista Testolin, Isabell Schneider and Dr. Verena Fetz for fruitful discussions and for proofreading of the manuscript.


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© Springer International Publishing AG 2016

Authors and Affiliations

  1. 1.Department of Chemical BiologyHelmholtz Centre for Infection ResearchBraunschweigGermany

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