Recent developments of the β-ketoacyl-acyl carrier protein synthase III (FabH) inhibitors: Emerging indication as...

Area of Science:

• Microbiology
• Medicinal Chemistry
• Drug Discovery

Background:

• Antimicrobial drug resistance (AMR) is a significant global health challenge, reducing treatment effectiveness for infections.
• Mutations in drug targets are a primary mechanism for microbial resistance to antibiotics.
• Novel therapeutic targets are crucial to combat the rising tide of antibiotic resistance.

Purpose of the Study:

• To review recent (2016-2025) antibacterial inhibitors targeting the β-ketoacyl-acyl carrier protein synthase III (FabH) enzyme.
• To explore diverse classes of FabH inhibitors, including synthetic compounds, metal complexes, natural products, nanoparticles, and dual-action agents.
• To provide researchers with insights for developing novel antibacterial agents by targeting FabH.

Main Methods:

• Literature review of scientific publications from 2016 to 2025.
• Analysis of various categories of antibacterial FabH inhibitors.
• Categorization of inhibitors into synthetic, metal complexes, natural, nanoparticles, and dual inhibitors.

Main Results:

• Several synthetic inhibitors (triazole, carbazole, indole, pyrazole, dioxepine derivatives) demonstrated potent bacterial FabH inhibition.
• Metal complexes (Fe, Cu) and zinc oxide nanoparticles showed significant FabH inhibitory activity.
• The study identified diverse chemical scaffolds with potential as antibacterial agents targeting FabH.

Conclusions:

• Targeting the FabH enzyme is a viable strategy for developing new antibiotics to overcome AMR.
• Various classes of compounds, including synthetic molecules and metal-based agents, show promise in inhibiting FabH.
• This review serves as a valuable resource for researchers focused on discovering novel antibacterial therapies.