Molecular Targets of β-Lactam-Based Antimicrobials: Beyond the Usual Suspects.
Molecular Targets of β-Lactam-Based Antimicrobials: Beyond the Usual Suspects.
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DOI：
10.3390/antibiotics3020128
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发表时间：
2014-04-03
期刊：
影响因子：
--
通讯作者：
Konaklieva MI
中科院分区：
文献类型：
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作者：
Konaklieva MI
抗菌药物开发的常见做法是，一旦检测到对该抗生素的耐药性，就迅速尝试为特定抗生素找到更稳定和广谱的变体。我们现在正面临着细菌对临床相关抗生素的耐药性，这种耐药性如此严重，以至于抗菌药物开发的对话应该包括具有替代作用机制的有效新抗生素。亲电β-内酰胺环通过对核心支架进行适当的修饰而适合于抑制不同的酶类别。在内酰胺氮上缺乏可电离基团的单环β-内酰胺表现出对细菌酶的靶向偏好，这些酶对耐药性和毒力很重要。本综述旨在引起人们对β-内酰胺类抗生素作为具有“不寻常”分子靶点的抗菌剂的多功能性的关注。
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.