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<p>The worldwide spread of antimicrobial resistance (AMR) is a considerable challenge to global health, resulting in a substantial depletion of human and material resources. Conventional antimicrobial agents are often ineffective against contemporary resistant strains, making the identification of novel drug targets a priority in antimicrobial development. Inhibition of the bacterial type II fatty acid synthesis (FAS-II) pathway is recognized as an effective antimicrobial strategy. β-Ketoacyl-ACP synthase III (FabH), a crucial enzyme in the FAS-II, presents potential as a target for next-generation antimicrobial agents. In recent years (2006–2025), research on synthetic small-molecule inhibitors targeting FabH has attracted widespread attention among scientists. However, reviews on FabH inhibitors remain scarce, with reports scattered across the literature. This paper outlines the attributes of FabH in various bacterial species and compiles the currently documented synthetic inhibitors. It examines the inhibitory effects of various core structures on FabH and analyzes the structure-activity relationships of specific compounds, including triazoles, carbazoles, indoles, and pyrazoles, etc. The goal is to offer innovative perspectives for the future development and formulation of antibacterial agents targeting FabH.</p><p></p>

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FabH (β-Ketoacyl-ACP Synthase III) -- Promising Novel Antibacterial Target and Its Inhibitors

  • 期刊论文

  • 发表日期：

    2026年2月4日

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  • Gui-Wen Li,
  • Qing-Yun Rong,
  • Wen Zhang,
  • Guo-Wu Rao,
  • Quan Zheng

摘要

The worldwide spread of antimicrobial resistance (AMR) is a considerable challenge to global health, resulting in a substantial depletion of human and material resources. Conventional antimicrobial agents are often ineffective against contemporary resistant strains, making the identification of novel drug targets a priority in antimicrobial development. Inhibition of the bacterial type II fatty acid synthesis (FAS-II) pathway is recognized as an effective antimicrobial strategy. β-Ketoacyl-ACP synthase III (FabH), a crucial enzyme in the FAS-II, presents potential as a target for next-generation antimicrobial agents. In recent years (2006–2025), research on synthetic small-molecule inhibitors targeting FabH has attracted widespread attention among scientists. However, reviews on FabH inhibitors remain scarce, with reports scattered across the literature. This paper outlines the attributes of FabH in various bacterial species and compiles the currently documented synthetic inhibitors. It examines the inhibitory effects of various core structures on FabH and analyzes the structure-activity relationships of specific compounds, including triazoles, carbazoles, indoles, and pyrazoles, etc. The goal is to offer innovative perspectives for the future development and formulation of antibacterial agents targeting FabH.