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

Antimicrobial drug resistance (AMR) compromises the effectiveness of treatments for various infections. It is a serious and growing threat to public health worldwide. Mutations in drug targets are a critical mechanism by which microorganisms develop resistance to antimicrobial agents. These genetic changes can potentially reduce the effectiveness of antibiotics. The increasing problem of antibiotic resistance has spurred global research efforts to identify novel treatment targets that outmanoeuvre resistant microorganisms. Targeting the β-ketoacyl-acyl carrier protein synthase III (FabH) can be a promising strategy to fight AMR because it is a selective bacterial target and has a defined metabolic involvement in the manufacture of critical pathogenic fatty acids that act as a precursor for bacterial membrane lipids. Consequently, this study has focused on several categories of newly reported (2016-2025) antibacterial FabH inhibitors, including synthetic, metal complexes, natural, nanoparticles, and dual inhibitors. Different synthetic inhibitors such as triazole, carbazole, indole, pyrazole, dioxepine etc. showed strong bacterial FabH inhibitory effect. Further, few metal complexes of Fe and Cu metals and zinc oxide composite nanoparticle also demonstrated good FabH targeted potency. Consequently, the present review will be helpful for the researchers involved in the discovery of more effective antibacterial agents by targeting the FabH enzyme.

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