Evaluation of Enoyl-ACP Reductase (FabK) as a Narrow-Spectrum Drug Target.

, a pathobiont inhabiting the oral cavity, contributes to opportunistic diseases, such as periodontal diseases and gastrointestinal cancers, which involve microbiota imbalance. Broad-spectrum antimicrobial agents, while effective against infections, can exacerbate dysbiosis. This necessitates the discovery of more targeted narrow-spectrum antimicrobial agents.

evaluation of enoyl-ACP reductase II (FabK) inhibition by phenylimidazole unveils a promising narrow-spectrum antimicrobial strategy.

infection (CDI) is a leading cause of hospital-acquired diarrhea, which often stems from disruption of the gut microbiota by broad-spectrum antibiotics. The increasing prevalence of antibiotic-resistant strains, combined with disappointing clinical trial results for recent antibiotic candidates, underscores the urgent need for novel CDI antibiotics. To this end, we investigated enoyl ACP reductase (FabK), a crucial enzyme in fatty acid synthesis, as a drug target for microbiome-sparing antibiotics.

evaluation of enoyl-ACP reductase II (FabK) Inhibition by phenylimidazole unveils a promising narrow-spectrum antimicrobial strategy.

infection (CDI) is a leading cause of hospital-acquired diarrhea, which often stem from disruption of the gut microbiota by broad-spectrum antibiotics. The increasing prevalence of antibiotic-resistant strains, combined with disappointing clinical trials results for recent antibiotic candidates, underscore the urgent need for novel CDI antibiotics. To this end, we investigated enoyl ACP reductase (FabK), a crucial enzyme in fatty acid synthesis, as a drug target for microbiome-sparing antibiotics.

Synthesis and evaluation of phenylimidazole FabK inhibitors as new Anti-C. Difficile agents.

Previously, 1-((4-(4-bromophenyl)-1H-imidazol-2-yl)methyl)-3-(5-(pyridin-2-ylthio)thiazol-2-yl)urea bearing a p-bromine substitution was shown to possess selective inhibitory activity against the Clostridioides difficile enoyl-acyl carrier protein (ACP) reductase II enzyme, FabK. Inhibition of CdFabK by this compound translated to promising antibacterial activity in the low micromolar range. In these studies, we sought to expand our knowledge of the SAR of the phenylimidazole CdFabK inhibitor series while improving the potency of the compounds.