2. Academic Validation
  3. Design, synthesis and antibacterial activity of novel LpxC inhibitors containing 1,2,3-triazole moieties

Design, synthesis and antibacterial activity of novel LpxC inhibitors containing 1,2,3-triazole moieties

  • Bioorg Med Chem Lett. 2026 Feb 24:136:130590. doi: 10.1016/j.bmcl.2026.130590.
Fangyi Jiang 1,  Chenghong Zheng 1,  Ying Wang 1,  Xinxin Hu 1,  Xuefu You 1,  Yucheng Wang 2,  Mei Zhu 1,  Minghua Wang 3,  Guoning Zhang 4,  Juxian Wang 5
Affiliations

Affiliations

  • 1 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
  • 2 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China.
  • 3 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
  • 4 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
  • 5 Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China; State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, China. Electronic address: [email protected].
PMID: 41747910 DOI: 10.1016/j.bmcl.2026.130590
Abstract

Two series of N-aryl-L-threonine derivatives bearing a triazole fragment are described as LpxC inhibitors targeting Gram-negative pathogens. Most compounds demonstrated stronger Antibacterial activities against E. coli (MICs: ≤0.03-16 μg/mL). Compounds a5, b1 and b2 exhibited pronounced Antibacterial activity against Escherichia coli (MICs: ≤0.03-0.5 μg/mL), Klebsiella pneumoniae (MICs: 1-16 μg/mL), and Pseudomonas aeruginosa (MICs: 1-8 μg/mL). Meanwhile, a5 displayed the lowest cytotoxicity toward A549 (IC50 > 4.032 μg/mL), HepG2 (IC50 > 4.032 μg/mL), and HEK293 (IC50 > 0.9112 ± 0.3461 μg/mL) mammalian cells. Against all tested E. coli strains, a5 displayed a therapeutic index of 3.64-67.20. Molecular docking analyses revealed that a5 simultaneously chelated the catalytic zinc ion and established extensive non-covalent interactions within the LpxC active site. This study provides a basis for further research on 1,2,3-triazole compounds.

Keywords

1,2,3-Triazole; Antibacterial activity; Gram-negative pathogens; LpxC inhibitors.

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