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Molecular Targets of β-Lactam-Based Antimicrobials: Beyond the Usual Suspects

机译：基于β-内酰胺的抗菌剂的分子靶标：超出常规范围

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The common practice in antibacterial drug development has been to rapidly make an attempt to find ever-more stable and broad-spectrum variants for a particular antibiotic, once a drug resistance for that antibiotic is detected. We are now facing bacterial resistance toward our clinically relevant antibiotics of such a magnitude that the conversation for antimicrobial drug development ought to include effective new antibiotics with alternative mechanisms of action. The electrophilic β-lactam ring is amenable for the inhibition of different enzyme classes by a suitable decoration of the core scaffold. Monocyclic β-lactams lacking an ionizable group at the lactam nitrogen exhibit target preferences toward bacterial enzymes important for resistance and virulence. The present review intends to draw attention to the versatility of the β-lactams as antimicrobials with “unusual” molecular targets.
机译：一旦检测到特定抗生素的耐药性，抗菌药物开发的常规做法便是迅速尝试寻找特定抗生素的更加稳定和广谱的变体。我们现在正面临着对我们临床相关抗生素的细菌耐药性，其程度如此之大，以至于抗菌药物开发的话题应包括具有替代作用机制的有效新抗生素。亲电的β-内酰胺环适于通过核心支架的适当装饰来抑制不同的酶类别。在内酰胺氮上缺乏可离子化基团的单环β-内酰胺类药物，对具有重要抵抗力和毒力的细菌酶表现出目标偏好。本文旨在提请人们注意β-内酰胺类作为具有“非常规”分子靶标的抗菌剂的多功能性。

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