1. Academic Validation
  2. Development and Antibacterial Properties of 4-[4-(Anilinomethyl)-3-phenylpyrazol-1-yl]benzoic Acid Derivatives as Fatty Acid Biosynthesis Inhibitors

Development and Antibacterial Properties of 4-[4-(Anilinomethyl)-3-phenylpyrazol-1-yl]benzoic Acid Derivatives as Fatty Acid Biosynthesis Inhibitors

  • J Med Chem. 2023 Oct 12;66(19):13622-13645. doi: 10.1021/acs.jmedchem.3c00969.
Subrata Roy 1 Hansa Raj Kc 1 Justin Roberts 1 Jared Hastings 1 David F Gilmore 2 Robert C Shields 2 Mohammad A Alam 1
Affiliations

Affiliations

  • 1 Department of Chemistry and Physics, College of Science and Mathematics, Arkansas State University, Jonesboro, Arkansas 72467, United States.
  • 2 Department of Biological Sciences, College of Science and Mathematics, Arkansas State University, Jonesboro, Arkansas 72467, United States.
Abstract

A number of novel pyrazole derivatives have been synthesized, and several of these compounds are potent Antibacterial agents with minimum inhibitory concentrations as low as 0.5 μg/mL. Human cell lines were tolerant to these lead compounds, and they showed negligible hemolytic effects at high concentrations. These bactericidal compounds are very effective against Bacterial growth in both planktonic and biofilm contexts. Various techniques were applied to show the inhibition of biofilm growth and eradication of preformed biofilms by lead compounds. Potent compounds are more effective against persisters than positive controls. In vivo studies revealed that lead compounds are effective in rescuing C. elegans from Bacterial infections. Several methods were applied to determine the mode of action including membrane permeability assay and SEM micrograph studies. Furthermore, CRISPRi studies led to the determination of these compounds as fatty acid biosynthesis (FAB) inhibitors.

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