{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T15:46:56Z","timestamp":1765208816849,"version":"3.46.0"},"reference-count":80,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82473771"],"award-info":[{"award-number":["82473771"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Key Project of Innovation Research 2035 Pilot Plan of Southwest University","award":["SWU-XDZD22007"],"award-info":[{"award-number":["SWU-XDZD22007"]}]},{"name":"Chongqing Graduate Research Innovation Project","award":["CYS18114"],"award-info":[{"award-number":["CYS18114"]}]},{"name":"Key Project of Tianjin Municipal Natural Science Foundation of China","award":["24ZXZSSS00020"],"award-info":[{"award-number":["24ZXZSSS00020"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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 4 displayed a broad-spectrum antibacterial profile with low cytotoxicity and hemolysis. It could inhibit the proliferation of methicillin-resistant Staphylococcus aureus and reduce its metabolic activity with low bacterial resistance. Further investigations revealed that the highly active compound 4 could not only disrupt cell membrane integrity and induce excessive reactive oxygen species within bacterial membranes, but also intercalate into DNA to form a supramolecular 4-DNA gyrase complex and cause cell death. These results demonstrated that compound 4 should have large potential as a promising candidate in the ongoing battle against resistant bacterial infections.<\/jats:p>","DOI":"10.3390\/ijms262411836","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"11836","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Heteroaryl Bishydrazono Nitroimidazoles: A Unique Structural Skeleton with Potent Multitargeting Antibacterial Activity"],"prefix":"10.3390","volume":"26","author":[{"given":"Zhen-Zhen","family":"Li","sequence":"first","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, Frontiers Science Center for Cell Responses, College of Pharmacy, Nankai University, Tianjin 300071, China"},{"name":"Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3233-5465","authenticated-orcid":false,"given":"Cheng-He","family":"Zhou","sequence":"additional","affiliation":[{"name":"Key Laboratory of Applied Chemistry of Chongqing Municipality, Institute of Bioorganic & Medicinal Chemistry, School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi-Jin","family":"Liu","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Medicinal Chemical Biology, Frontiers Science Center for New Organic Matter, Frontiers Science Center for Cell Responses, College of Pharmacy, Nankai University, Tianjin 300071, China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1126\/science.ado5186","article-title":"China\u2019s plan to combat antimicrobial resistance","volume":"383","author":"Li","year":"2024","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/d41586-024-02601-4","article-title":"Five ways science is tackling the antibiotic resistance crisis","volume":"632","author":"Dance","year":"2024","journal-title":"Nature"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1700","DOI":"10.1002\/med.22115","article-title":"Comprehensive insights into sulfanilamido-based medicinal design and research","volume":"45","author":"Wang","year":"2025","journal-title":"Med. Res. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1038\/s41579-024-01105-2","article-title":"Bloodstream infections: Mechanisms of pathogenesis and opportunities for intervention","volume":"23","author":"Holmes","year":"2025","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1038\/s41579-018-0147-4","article-title":"Methicillin-resistant Staphylococcus aureus: An overview of basic and clinical research","volume":"17","author":"Turner","year":"2019","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"18033","DOI":"10.1038\/nrdp.2018.33","article-title":"Methicillin-resistant Staphylococcus aureus","volume":"4","author":"Lee","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Gehrmann, R., Hertlein, T., Hopke, E., Ohlsen, K., Lalk, M., and Hilgeroth, A. (2021). Novel small-molecule hybrid-antibacterial agents against S. aureus and MRSA strains. Molecules, 27.","DOI":"10.3390\/molecules27010061"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Larsson, D.J., and Flach, C.F. (2022). Antibiotic resistance in the environment. Nat. Rev. Microbiol., 20.","DOI":"10.1038\/s41579-021-00649-x"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e51034","DOI":"10.15252\/embr.202051034","article-title":"Antibiotic resistance and persistence-implications for human health and treatment perspectives","volume":"21","author":"Huemer","year":"2020","journal-title":"EMBO Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7515","DOI":"10.2147\/IDR.S428837","article-title":"Potential causes of spread of antimicrobial resistance and preventive measures in one health perspective\u2014A review","volume":"16","author":"Endale","year":"2023","journal-title":"Infect. Drug Resist."},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Li, S.R., Tan, Y.M., Zhang, L., and Zhou, C.H. (2023). Comprehensive insights into medicinal research on imidazole-based supramolecular complexes. Pharmaceutics, 15.","DOI":"10.3390\/pharmaceutics15051348"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/med.21290","article-title":"Comprehensive review in current developments of imidazole-based medicinal chemistry","volume":"34","author":"Zhang","year":"2014","journal-title":"Med. Res. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Zarenezhad, E., Behmard, E., Karami, R., Behrouz, S., Marzi, M., Ghasemian, A., and Rad, M.N.S. (2024). The antibacterial and anti-biofilm effects of novel synthetized nitroimidazole compounds against methicillin-resistant Staphylococcus aureus and carbapenem-resistant Escherichia coli and Klebsiella pneumonia In Vitro and In Silico. BMC Chem., 18.","DOI":"10.1186\/s13065-024-01333-w"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11349","DOI":"10.1021\/acs.jmedchem.8b01578","article-title":"Design, synthesis, and biological evaluation of 2 nitroimidazopyrazin-one\/-es with antitubercular and antiparasitic activity","volume":"61","author":"Jarrad","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"10860","DOI":"10.1021\/acs.jmedchem.8b01504","article-title":"4-Hydroxy-3-nitro-5-ureido-benzenesulfonamides selectively target the tumor-associated carbonic anhydrase isoforms IX and XII showing hypoxia-enhanced antiproliferative profiles","volume":"61","author":"Nocentini","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1360\/N032018-00098","article-title":"Researches and applications of nitroimidazole heterocycles in medicinal chemistry","volume":"49","author":"Li","year":"2019","journal-title":"Sci. Sin. Chim."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Rocha-Gardu\u00f1o, G., Hern\u00e1ndez-Mart\u00ednez, N.A., Col\u00edn-Lozano, B., Estrada-Soto, S., Hern\u00e1ndez-N\u00fa\u00f1ez, E., Prieto-Mart\u00ednez, F.D., Medina-Franco, J.L., Chale-Dzul, J.B., Moo-Puc, R., and Navarrete-V\u00e1zquez, G. (2020). Metronidazole and secnidazole carbamates: Synthesis, antiprotozoal activity, and molecular dynamics studies. Molecules, 25.","DOI":"10.3390\/molecules25040793"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1164","DOI":"10.1080\/14756366.2019.1626375","article-title":"Appraisal of anti-protozoan activity of nitroaromatic benzenesulfonamides inhibiting carbonic anhydrases from Trypanosoma cruzi and Leishmania donovani","volume":"34","author":"Nocentini","year":"2019","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"7636","DOI":"10.1021\/acs.jmedchem.7b00143","article-title":"Nitroimidazoles: Molecular fireworks that combat a broad spectrum of infectious diseases","volume":"60","author":"Ang","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"14715","DOI":"10.1021\/acsnano.0c00764","article-title":"Electron-accepting micelles deplete reduced nicotinamide adenine dinucleotide phosphate and impair two antioxidant cascades for ferroptosis-induced tumor eradication","volume":"14","author":"Guo","year":"2020","journal-title":"ACS Nano"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2851","DOI":"10.1021\/acs.jmedchem.8b00147","article-title":"Nitro-group-containing drugs","volume":"62","author":"Nepali","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"112994","DOI":"10.1016\/j.ejmech.2020.112994","article-title":"Metronidazole-conjugates: A comprehensive review of recent developments towards synthesis and medicinal perspective","volume":"210","author":"Patel","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"3120","DOI":"10.1016\/j.bmc.2013.03.023","article-title":"Design, synthesis and antimicrobial activities evaluation of Schiff base derived from secnidazole derivatives as potential FabH inhibitors","volume":"21","author":"Li","year":"2013","journal-title":"Bioorg Med. Chem."},{"key":"ref_24","first-page":"47","article-title":"Some Nitroimidazole Derivatives as Antibacterial and Antifungal Agents in In Vitro Study","volume":"1","author":"Olender","year":"2019","journal-title":"J. Med. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"123","DOI":"10.3109\/14756361003733654","article-title":"Synthesis and antileishmanial activity of 5-(5-nitroaryl)-2-substituted-thio-1,3,4-thiadiazoles","volume":"26","author":"Alipour","year":"2010","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"ref_26","first-page":"883","article-title":"ALDH2 mediates 5-nitrofuran activity in multiple species","volume":"19","author":"Zhou","year":"2012","journal-title":"Cell Chem. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"723","DOI":"10.1016\/j.ejmech.2019.06.093","article-title":"Indole-nitroimidazole conjugates as efficient manipulators to decrease the genes expression of methicillin-resistant Staphylococcus aureus","volume":"179","author":"Li","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"393","DOI":"10.1016\/j.ejmech.2018.04.059","article-title":"New developments in non-quinolone-based antibiotics for the inhibiton of bacterial gyrase and topoisomerase IV","volume":"152","author":"Badshah","year":"2018","journal-title":"Eur. J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1325","DOI":"10.2174\/092986710790936284","article-title":"Coumarins: Old compounds with novel promising therapeutic perspectives","volume":"17","author":"Riveiro","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"7557","DOI":"10.3390\/molecules18077557","article-title":"New 7-[4-(4-(un) substituted) piperazine-1-carbonyl]-piperazin-1-yl] derivatives of fluoroquinolone: Synthesis and antimicrobial evaluation","volume":"18","author":"Chen","year":"2013","journal-title":"Molecules"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"630","DOI":"10.2174\/1389557515666150709111342","article-title":"Carbazole derivatives: A promising scenario for breast cancer treatment","volume":"16","author":"Caruso","year":"2016","journal-title":"Mini Rev. Med. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"8932","DOI":"10.1021\/acs.jmedchem.4c00209","article-title":"A unique hybridization route to access hydrazylnaphthalimidols as novel structural scaffolds of multitargeting broad-spectrum antifungal candidates","volume":"67","author":"Wang","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3900","DOI":"10.1080\/00958972.2011.634005","article-title":"DNA-binding, oxidative DNA cleavage, and coordination mode of later 3d transition metal complexes of a Schiff base derived from isatin as antimicrobial agents","volume":"64","author":"Raman","year":"2011","journal-title":"J. Coord. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"342","DOI":"10.2174\/1389557519666191014142448","article-title":"Synthesis and Biological Activity of Hydrazones and Derivatives: A Review","volume":"20","author":"Brum","year":"2020","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"494","DOI":"10.1038\/nchem.328","article-title":"Metal-free carbon\u2013carbon bond-forming reductive coupling between boronic acids and tosylhydrazones","volume":"1","author":"Barluenga","year":"2009","journal-title":"Nat. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1006","DOI":"10.1016\/j.msec.2017.04.152","article-title":"DNA interaction, antioxidant and in vitro cytotoxic activities of some mononuclear metal(II) complexes of a bishydrazone ligand","volume":"78","author":"Dhanaraj","year":"2017","journal-title":"Mat. Sci. Eng. C-Mater."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"108396","DOI":"10.1016\/j.cclet.2023.108396","article-title":"Recent advances in the synthesis and applications of furocoumarin derivatives","volume":"34","author":"Chen","year":"2023","journal-title":"Chin. Chem. Lett."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"115701","DOI":"10.1016\/j.ejmech.2023.115701","article-title":"Heterocyclic pyrimidine derivatives as promising antibacterial agents","volume":"259","author":"Ahmed","year":"2023","journal-title":"Eur. J. Med. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1002\/bkcs.11049","article-title":"Synthesis of (3-(2-Aminopyrimidin-4-yl)-4-hydroxyphenyl)phenyl Methanone Analogues as Inhibitors of Vascular Endothelial Growth Factor Receptor-2 Kinase","volume":"38","author":"More","year":"2017","journal-title":"Bull. Korean Chem. Soc."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"11019","DOI":"10.1021\/acs.jafc.1c08383","article-title":"Trifluoromethylpyridine: An important active fragment for the discovery of new pesticides","volume":"70","author":"Zheng","year":"2022","journal-title":"J. Agric. Food Chem."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.ejmech.2017.03.025","article-title":"Recent synthetic and medicinal perspectives of dihydropyrimidinones: A review","volume":"132","author":"Kaur","year":"2017","journal-title":"Eur. J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1210","DOI":"10.1038\/s41467-020-15039-9","article-title":"The electronic structure of benzene from a tiling of the correlated 126-dimensional wavefunction","volume":"11","author":"Liu","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1007\/s41061-025-00503-1","article-title":"Exploring the structural versatility and dynamic behavior of acyl\/aroyl hydrazones: A comprehensive review","volume":"383","author":"Kadyan","year":"2025","journal-title":"Top. Curr. Chem."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.chemphys.2017.03.011","article-title":"Comparison between nitroxide and hydrazyl free radicals in selective alcohols oxidation","volume":"490","author":"Shakir","year":"2017","journal-title":"Chem. Phys."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1007\/s41061-024-00468-7","article-title":"Significance of chalcone scaffolds in medicinal chemistry","volume":"382","author":"Mazumder","year":"2024","journal-title":"Top. Curr. Chem."},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Tok, F., Sa\u011fl\u0131k, B.N., \u00d6zkay, Y., Ilg\u0131n, S., Kaplanc\u0131kl\u0131, Z.A., and Ko\u00e7yi\u011fit-Kaymak\u00e7\u0131o\u011flu, B. (2021). Synthesis of new hydrazone derivatives and evaluation of their monoamine oxidase inhibitory activity. Bioorg Chem., 114.","DOI":"10.1016\/j.bioorg.2021.105038"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"108207","DOI":"10.1016\/j.cclet.2023.108207","article-title":"Hydrazone derivatives in agrochemical discovery and development","volume":"35","author":"Wang","year":"2024","journal-title":"Chin. Chem. Lett."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"113340","DOI":"10.1016\/j.ejmech.2021.113340","article-title":"Membrane active 7-thiazoxime quinolones as novel DNA binding agents to decrease the genes expression and exert potent anti-methicillin-resistant Staphylococcus aureus activity","volume":"217","author":"Chen","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.ccr.2019.03.010","article-title":"Recent Developments in Penta-, Hexa-, and Heptadentate Schiff Base Ligands and Their Metal Complexes","volume":"389","author":"Liu","year":"2019","journal-title":"Coordin Chem. Rev."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1016\/j.ijantimicag.2016.06.026","article-title":"Ex vivo efficacy of gemifloxacin in experimental keratitis induced by methicillin-resistant Staphylococcus aureus","volume":"48","author":"Marino","year":"2016","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"20257","DOI":"10.1021\/jacs.0c10771","article-title":"Molecular sizes and antibacterial performance relationships of flexible ionic liquid derivatives","volume":"142","author":"Zheng","year":"2020","journal-title":"J. Am. Chem. Soc."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/j.jcis.2020.09.041","article-title":"Antifouling and antibacterial behavior of membranes containing quaternary ammonium and zwitterionic polymers","volume":"584","author":"Zhu","year":"2021","journal-title":"J. Colloid. Interface Sci."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1039\/C7QO00836H","article-title":"Pyridinium salts: From synthesis to reactivity and applications","volume":"5","author":"Sowmiah","year":"2018","journal-title":"Org. Chem. Front."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"7630","DOI":"10.1021\/acs.jmedchem.1c00334","article-title":"Identification of unique quinazolone thiazoles as novel structural scaffolds for potential Gram-negative bacterial conquerors","volume":"64","author":"Wang","year":"2021","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"eabn0771","DOI":"10.1126\/sciadv.abn0771","article-title":"Switching from membrane disrupting to membrane crossing, an effective strategy in designing antibacterial polypeptide","volume":"9","author":"Zhang","year":"2023","journal-title":"Sci. Adv."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Li, S.R., Yu, J.C., Cheng, Y., and Zhou, C.H. (2025). Discovery of benzopyronyl imidazolidinediones as new structural skeleton of potential multitargeting antibacterial agents. Bioorg Chem., 26.","DOI":"10.1016\/j.bioorg.2025.108923"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1680","DOI":"10.1038\/s41589-024-01685-3","article-title":"Macrolones target bacterial ribosomes and DNA gyrase and can evade resistance mechanisms","volume":"20","author":"Aleksandrova","year":"2024","journal-title":"Nat. Chem. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1021\/acs.jmedchem.1c01592","article-title":"Natural berberine-derived azolyl ethanols as new structural antibacterial agents against drug-resistant Escherichia coli","volume":"65","author":"Sun","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"939","DOI":"10.1038\/s41564-025-01968-y","article-title":"A quinolone N-oxide antibiotic selectively targets Neisseria gonorrhoeae via its toxin-antitoxin system","volume":"10","author":"Mix","year":"2025","journal-title":"Nat. Microbiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Ibrahim, S.A., Fayed, E.A., Rizk, H.F., Desouky, S.E., and Raga, A. (2021). Hydrazonoyl bromide precursors as DHFR inhibitors for the synthesis of bis-thiazolyl pyrazole derivatives; antimicrobial activities, antibiofilm, and drug combination studies against MRSA. Bioorg Chem., 116.","DOI":"10.1016\/j.bioorg.2021.105339"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"114874","DOI":"10.1016\/j.addr.2023.114874","article-title":"New antifungal strategies: Drug combination and co-delivery","volume":"198","author":"Zhu","year":"2023","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"20458","DOI":"10.1021\/acsami.3c03091","article-title":"Amphiphilic nano-swords for direct penetration and eradication of pathogenic bacterial biofilms","volume":"15","author":"Zhou","year":"2023","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"4910","DOI":"10.1021\/acs.jmedchem.2c02042","article-title":"Azolylpyrimidinediols as novel structural scaffolds of DNA-groove binders against intractable Acinetobacter baumannii","volume":"66","author":"Tan","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"608","DOI":"10.1038\/s41579-022-00767-0","article-title":"The biofilm life cycle: Expanding the conceptual model of biofilm formation","volume":"20","author":"Sauer","year":"2022","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"eabc9917","DOI":"10.1126\/sciadv.abc9917","article-title":"A polymeric approach toward resistance-resistant antimicrobial agent with dual-selective mechanisms of action","volume":"7","author":"Bai","year":"2021","journal-title":"Sci. Adv."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"5061","DOI":"10.1021\/acs.jmedchem.2c02135","article-title":"Discovery of quaternized pyridine-thiazole-pleuromutilin derivatives with broad-spectrum antibacterial and potent anti-MRSA activity","volume":"66","author":"Xia","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"13985","DOI":"10.1021\/acs.jafc.5c00554","article-title":"Heteroarylcyanovinyl benzimidazoles as new antibacterial skeleton with large potential to combat bacterial infections","volume":"73","author":"Li","year":"2025","journal-title":"J. Agric. Food Chem."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"eaba3571","DOI":"10.1126\/scitranslmed.aba3571","article-title":"Bacteria-specific phototoxic reactions triggered by blue light and phytochemical carvacrol","volume":"13","author":"Lu","year":"2021","journal-title":"Sci. Transl. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"422","DOI":"10.1089\/rej.2014.1555","article-title":"Recrystallization of dihydromyricetin from Ampelopsis grossedentata and its anti-oxidant activity evaluation","volume":"17","author":"Liao","year":"2014","journal-title":"Rejuvenation Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"E2100","DOI":"10.1073\/pnas.1401876111","article-title":"Antibiotics induce redox-related physiological alterations as part of their lethality","volume":"111","author":"Dwyer","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5685","DOI":"10.1038\/s41467-022-33301-0","article-title":"A protein-based cGAS-STING nanoagonist enhances T cell-mediated anti-tumor immune responses","volume":"13","author":"Wang","year":"2022","journal-title":"Nat Commun."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1038\/nrc3803","article-title":"Mitochondrial ROS in cancer: Initiators, amplifiers or an Achilles\u2019 heel?","volume":"14","author":"Sabharwal","year":"2014","journal-title":"Nat. Rev. Cancer"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"3071","DOI":"10.1007\/s11426-024-2228-4","article-title":"Chemical biology investigation of a triple-action, smart-decomposition antimicrobial booster based-combination therapy against \u201cESKAPE\u201d pathogens","volume":"67","author":"Wang","year":"2024","journal-title":"Sci. China Chem."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"9028","DOI":"10.1021\/acs.jmedchem.4c00238","article-title":"Cyanomethylquinolones as a new class of potential multitargeting broad-spectrum antibacterial agents","volume":"67","author":"Tan","year":"2024","journal-title":"J. Med. Chem."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2291","DOI":"10.1021\/acsinfecdis.2c00365","article-title":"Discovery of new anti-MRSA agents based on phenoxyethanol and its mechanism","volume":"8","author":"Xie","year":"2022","journal-title":"ACS Infect. Dis."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"4131","DOI":"10.1021\/acs.jmedchem.2c02126","article-title":"New apoptosis inducers containing anti-inflammatory drugs and pnictogen derivatives: A new strategy in the development of mitochondrial targeting chemotherapeutics","volume":"66","author":"Banti","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1039\/a705982e","article-title":"DNA minor-groove recognition by small molecules","volume":"18","author":"Neidle","year":"2001","journal-title":"Nat. Prod. Rep."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1038\/nrmicro3155","article-title":"Ribosome-targeting antibiotics and mechanisms of bacterial resistance","volume":"12","author":"Wilson","year":"2014","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"6040","DOI":"10.1021\/acs.chemrev.8b00520","article-title":"Mechanistic landscape of membrane-permeabilizing peptides","volume":"119","author":"Guha","year":"2019","journal-title":"Chem. Rev."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"2457","DOI":"10.1038\/s41467-020-16600-2","article-title":"Mode of action of teixobactins in cellular membranes","volume":"11","author":"Shukla","year":"2020","journal-title":"Nat. Commun."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11836\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:53:34Z","timestamp":1765205614000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/24\/11836"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,8]]},"references-count":80,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2025,12]]}},"alternative-id":["ijms262411836"],"URL":"https:\/\/doi.org\/10.3390\/ijms262411836","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,12,8]]}}}