ORIGINAL RESEARCH article
Front. Chem.
Sec. Medicinal and Pharmaceutical Chemistry
Volume 13 - 2025 | doi: 10.3389/fchem.2025.1654358
Membrane-Targeting Antibacterial Isoniazid Schiff Base against S. aureus and Biofilms
Provisionally accepted
- The Second Hospital of Qinhuangdao, Qinhuangdao, China
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Drawing upon prior research, we successfully replicated a series of isoniazid-derived hydrazone derivatives. The lead compound C5, exhibited potent antibacterial activity against Gram-positive bacteria (especially Staphylococcus aureus ATCC 29213, MIC = 16 μg/mL), with no hemolysis and low cytotoxicity (VERO IC₅₀ > 128 μg/mL). C5 achieved complete eradication of S. aureus within 16 h at 8 × MIC and showed low resistance induction. Mechanistic studies revealed bacterial membrane disruption by C5, evidenced by membrane depolarization (DiSC35 fluorescence) and loss of integrity (SYTOX Green uptake), causing protein/DNA leakage. Concurrently, C5 induced ROS accumulation and significantly reduced ATP levels. Notably, C5 suppressed LPS-induced NO/TNF-α release in macrophages (p < 0.01) and inhibited/disrupted S. aureus biofilms. These findings demonstrate C5's multifunctional action: direct bactericidal activity via membrane targeting, anti-biofilm efficacy, and immunomodulation, highlighting its promise against resistant infections.
Keywords: Isoniazid, Schiff base, Antibacterial activity, Anti biofilm, Anti inflammatory
Received: 26 Jun 2025; Accepted: 26 Aug 2025.
Copyright: © 2025 Liu, Hu, Liu and Qu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Yaguang Liu, The Second Hospital of Qinhuangdao, Qinhuangdao, China
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