Iminocarbamoyl-hybridized nitrofuranylcoumarins as broad-spectrum antibacterial agents with multitargeting potential

  • Eur J Med Chem. 2026 Jul 5:311:118819. doi: 10.1016/j.ejmech.2026.118819.
Shi-Yu Huang  1 ,  Nisar Ahmad  1 ,  Jia-Chen Yu  1 ,  Qian Cheng  2 ,  Shao-Lin Zhang  3 ,  Cheng-He Zhou  4
Affiliations
  • 1. Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China.
  • 2. Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China. Electronic address: [email protected].
  • 3. School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing, 401331, PR China. Electronic address: [email protected].
  • 4. Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing, 400715, PR China. Electronic address: [email protected].
PMID: 41946013 DOI: 10.1016/j.ejmech.2026.118819
Abstract

In this work, a unique type of iminocarbamoyl-hybridized nitrofuranylcoumarins (INs) with multitargeting broad-spectrum Antibacterial potential was developed. Most of INs exhibited potent Antibacterial potency against the tested Bacterial strains; Especially, IN 6a displayed strong activities against MRSA and Klebsiella pneumoniae (MICs = 0.03 and 0.06 μg/mL), being 32- and 16-fold more effective than ciprofloxacin. The highly active IN 6a demonstrated favorable druggability without obvious resistance, hemolysis and cytotoxicity, as well as rapid bactericidal ability. Preliminary mechanistic studies revealed that IN 6a could not only disrupt cell membranes, but also cause the accumulation of Reactive Oxygen Species, which led to metabolic disruption and Bacterial death. Moreover, IN 6a could bind with DNA gyrase through various noncovalent interactions, thereby affecting its normal function and inducing cell death. Furthermore, IN 6a displayed superior anti-MRSA efficacy to nifuroxazide and norfloxacin in vivo. These findings suggested that INs are promising multitargeting Antibacterial agents to combat global Bacterial resistance.

Keywords
Antibacterial; Coumarin; DNA; Nitrofuran; ROS.
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