biostudies-literatureLi ZZKey Project of Innovation Research 2035 Pilot Plan of Southwest UniversityNational Natural Science Foundation of Chinathe Key Project of Tianjin Municipal Natural Science Foundation of ChinaChongqing Graduate Research Innovation Project11836https://www.ebi.ac.uk/biostudies/studies/S-EPMC12733231biostudies-literatureUnknown26(24)The emergence of bacterial infections as a critical public health challenge underscores the urgent need for innovative therapeutic strategies. We designed and synthesized a series of novel heteroaryl bishydrozono nitroimidazoles and their analogs by strategically hybridizing multiple molecular components through diverse linkers. Among the newly synthesized compounds, compound <b>4</b> displayed a broad-spectrum antibacterial profile with low cytotoxicity and hemolysis. It could inhibit the proliferation of methicillin-resistant <i>Staphylococcus aureus</i> and reduce its metabolic activity with low bacterial resistance. Further investigations revealed that the highly active compound <b>4</b> could not only disrupt cell membrane integrity and induce excessive reactive oxygen species within International journal of molecular sciencesHeteroaryl Bishydrazono Nitroimidazoles: A Unique Structural Skeleton with Potent Multitargeting Antibacterial Activity.PMC1273323124ZXZSSS00020CYS18114SWU-XDZD2200782473771Liu YJZhou CHLi ZZfalseHeteroaryl Bishydrazono Nitroimidazoles: A Unique Structural Skeleton with Potent Multitargeting Antibacterial Activity.The emergence of bacterial infections as a critical public health challenge underscores the urgent need for innovative therapeutic strategies. We designed and synthesized a series of novel heteroaryl bishydrozono nitroimidazoles and their analogs by strategically hybridizing multiple molecular components through diverse linkers. Among the newly synthesized compounds, compound <b>4</b> displayed a broad-spectrum antibacterial profile with low cytotoxicity and hemolysis. It could inhibit the proliferation of methicillin-resistant <i>Staphylococcus aureus</i> and reduce its metabolic activity with low bacterial resistance. Further investigations revealed that the highly active compound <b>4</b> could not only disrupt cell membrane integrity and induce excessive reactive oxygen species within 2025-01-01T00:00:00Z2025 Dec2026-05-28T03:18:37.598Z2026-05-28T03:10:57.218ZS-EPMC127332314146526610.3390/ijms262411836