Naphthalimide-mediated multitargeting antibacterial actions to enhance efficacy and broaden antibacterial spectrum of nitroimidazolyl ethylalcohols
- Bioorg Chem. 2026 Jun 9:180:110076. doi: 10.1016/j.bioorg.2026.110076.
- 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. Institute of Bioorganic & Medicinal Chemistry, Key Laboratory of Applied Chemistry of Chongqing Municipality, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China; Chongqing Werlchem New Materials Technology Co., Ltd, Chongqing 401120, China. Electronic address: [email protected].
- 3. School of Pharmaceutical Sciences, Chongqing Key Laboratory of Natural Product Synthesis and Drug Research, Chongqing University, Chongqing 401331, China. Electronic address: [email protected].
- 4. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Zhongshan 528400, China. Electronic address: [email protected].
- 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: [email protected].
To combat the escalating challenge of Bacterial resistance, a novel class of naphthalimide-mediated nitroimidazolyl ethylalcohols (NNEs) was developed. Most of the prepared NNEs showed potent Antibacterial activities. Notably, nitrophenylamino NNE 37 g enhanced the activity of metronidazole against anaerobic bacteria and expanded its Antibacterial spectrum to aerobic bacteria (MICs = 0.25-4 μg/mL), being superior to ciprofloxacin and ceftizoxime. Structure-activity relationship analysis suggested that the nitroimidazolyl ethylalcohol fragment was essential for activity, whereas chirality showed negligible effect on Antibacterial efficacy. NNE 37 g also demonstrated low cytotoxicity, hemolysis, drug resistance and favorable plasma stability. Galleria mellonella Infection model further demonstrated its more potent anti-MRSA efficacy in vivo than ciprofloxacin. Moreover, NNE 37 g displayed multitargeting Antibacterial mechanisms, involving allosteric inhibition of PBP2a, DNA intercalation, and disruption of redox homeostasis via ROS/RNS overproduction, ultimately resulting in Bacterial cell death. This series of studies provides a promising prospect for the development of naphthalimide-mediated nitroimidazolyl ethylalcohols as potential Antibacterial candidates to tackle Bacterial infections.
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Cat. No.Product NameDescriptionTargetResearch Area
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target: Penicillin-binding protein (PBP); Bacterial; DNA Alkylator/Crosslinker; Reactive Oxygen Species (ROS)Research Areas: Infection