2. Academic Validation
  3. Benzo-α-pyrone-derived multitargeting actions to enhance the antibacterial performance of sulfanilamides against Escherichia coli

Benzo-α-pyrone-derived multitargeting actions to enhance the antibacterial performance of sulfanilamides against Escherichia coli

  • Bioorg Chem. 2025 May:158:108339. doi: 10.1016/j.bioorg.2025.108339.
Yi-Xin Wang 1,  Hao-Ran Wang 1,  Jiang-Sheng Zhao 1,  Xun-Cai Yang 1,  Bo Fang 2,  Zhong-Lin Zang 3,  Rong-Xia Geng 4,  Cheng-He Zhou 5
Affiliations

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, China.
  • 2 College of Pharmacy, National & Local Joint Engineering Research Center of Targeted and Innovative Therapeutics, Chongqing Key Laboratory of Kinase Modulators as Innovative Medicine, Chongqing University of Arts and Sciences, Chongqing 402160, China. Electronic address: fangbo2100@163.com.
  • 3 Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. Electronic address: zhonglinzang@swu.edu.cn.
  • 4 Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. Electronic address: geng0712@swu.edu.cn.
  • 5 Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China. Electronic address: zhouch@swu.edu.cn.
PMID: 40056605 DOI: 10.1016/j.bioorg.2025.108339
Abstract

A novel class of benzopyrone-sulfanilamide hybrids was synthesized from Phenols via multi-step reactions. Some prepared compounds effectively suppressed Bacterial growth at low concentrations, and especially, sulfanilamide-hybridized 2-methyl-5-nitroimidazolyl benzopyrone 11c exhibited significant inhibitory potency against Escherichia coli (MIC = 0.0022 mM), which was 11-fold more active than clinical norfloxacin. Furthermore, compound 11c showed negligible hemolytic activity, low cytotoxicity and no drug resistance. Mechanistic studies indicated that the highly active 11c disrupted Bacterial membrane integrity, reduced metabolic activity, bound DNA grooves to inhibit replication without the ability to cleave DNA, and induced Reactive Oxygen Species (ROS) accumulation, collectively leading to Bacterial death. These results highlight the potential of sulfanilamide-hybridized benzopyrones as multitarget Antibacterial agents, warranting further development to combat Bacterial infections.

Keywords

Antibacterial; Benzopyrone; Multitargeting; Resistance; Sulfonamide.

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