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

IF 4.5 2区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Bioorganic Chemistry Pub Date : 2025-03-05 DOI:10.1016/j.bioorg.2025.108339

Yi-Xin Wang , Hao-Ran Wang , Jiang-Sheng Zhao , Xun-Cai Yang , Bo Fang , Zhong-Lin Zang , Rong-Xia Geng , Cheng-He Zhou

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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.

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来源期刊

Bioorganic Chemistry 生物-生化与分子生物学

CiteScore

9.70

自引率

3.90%

发文量

679

审稿时长

31 days

期刊介绍： Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry. For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature. The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.