{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:54:25Z","timestamp":1785430465902,"version":"3.56.0"},"reference-count":56,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T00:00:00Z","timestamp":1779062400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Science and Higher Education of the Republic of Kazakhstan","award":["AP23490056"],"award-info":[{"award-number":["AP23490056"]}]},{"award":["AP23490056"],"award-info":[{"award-number":["AP23490056"]}],"id":[{"id":"https:\/\/ror.org\/05tyne317","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>A strategy to create highly effective antimicrobial agents was proposed based on the conjugation of three functional components: a cationic quaternary ammonium salt (QAS) that exerts a membrane-disrupting effect and promotes selective accumulation on bacterial surfaces; a phosphonamidate linker for controlled activation; and a sterically hindered phenol (SHP) fragment as a potential redox component. This approach enabled the preparation of 40 target phosphonamidate\u2013SHP\/QAS hybrids in high yields (88\u201398%). Evaluation of their antimicrobial activity against major pathogens and methicillin-resistant Staphylococcus aureus (MRSA) revealed high potency against Gram-positive bacteria. The lead compounds achieved minimum inhibitory concentration (MIC) values of 0.7\u20132.8 \u03bcM, which is up to 10 times lower than that of the reference drug, norfloxacin. Mechanistic studies confirmed that these hybrids disrupt the bacterial membrane. In addition, an increase in intracellular ROS levels was observed for the most active compound. The SHP\/QAS hybrids retained high activity against S. aureus ATCC 209P after 17 passages and showed low cytotoxicity (SI = 62\u201392) and negligible hemolysis. These properties indicate that this approach may offer a useful strategy for developing antibacterial agents with a potentially lower risk of inducing conventional resistance mechanisms.<\/jats:p>","DOI":"10.3390\/ijms27104524","type":"journal-article","created":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T07:35:43Z","timestamp":1779176143000},"page":"4524","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Phosphonamidates Integrating Sterically Hindered Phenols with Membrane-Active Cations: A Redox-Activated Approach to Antimicrobial Agents"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2615-9418","authenticated-orcid":false,"given":"Elmira","family":"Gibadullina","sequence":"first","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov St. 8, Kazan 420088, Russia"},{"name":"Laboratory of Engineering Profile \u201cPhysical and Chemical Methods of Analysis\u201d, Korkyt Ata Kyzylorda University, 29A, Aiteke Bi Street, Kyzylorda 120014, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-3223-2491","authenticated-orcid":false,"given":"Adel","family":"Shakirov","sequence":"additional","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov St. 8, Kazan 420088, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9346-5920","authenticated-orcid":false,"given":"Margarita","family":"Neganova","sequence":"additional","affiliation":[{"name":"Laboratory of Engineering Profile \u201cPhysical and Chemical Methods of Analysis\u201d, Korkyt Ata Kyzylorda University, 29A, Aiteke Bi Street, Kyzylorda 120014, Kazakhstan"},{"name":"A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Bld. 1., Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5370-3370","authenticated-orcid":false,"given":"Yulia","family":"Aleksandrova","sequence":"additional","affiliation":[{"name":"Laboratory of Engineering Profile \u201cPhysical and Chemical Methods of Analysis\u201d, Korkyt Ata Kyzylorda University, 29A, Aiteke Bi Street, Kyzylorda 120014, Kazakhstan"},{"name":"A.N. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, Vavilova St. 28, Bld. 1., Moscow 119334, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexandra","family":"Voloshina","sequence":"additional","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov St. 8, Kazan 420088, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2816-8142","authenticated-orcid":false,"given":"Anna","family":"Lyubina","sequence":"additional","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov St. 8, Kazan 420088, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anastasiya","family":"Sapunova","sequence":"additional","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov St. 8, Kazan 420088, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Strelnik","sequence":"additional","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov St. 8, Kazan 420088, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9720-7977","authenticated-orcid":false,"given":"Kamil","family":"Ivshin","sequence":"additional","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov St. 8, Kazan 420088, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6774-7449","authenticated-orcid":false,"given":"Assel","family":"Shuragaziyeva","sequence":"additional","affiliation":[{"name":"Laboratory of Engineering Profile \u201cPhysical and Chemical Methods of Analysis\u201d, Korkyt Ata Kyzylorda University, 29A, Aiteke Bi Street, Kyzylorda 120014, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9902-2546","authenticated-orcid":false,"given":"Altynkul","family":"Toibazarova","sequence":"additional","affiliation":[{"name":"Laboratory of Engineering Profile \u201cPhysical and Chemical Methods of Analysis\u201d, Korkyt Ata Kyzylorda University, 29A, Aiteke Bi Street, Kyzylorda 120014, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Banu","family":"Diyarova","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Institute of Natural Science, Kazakh National Women\u2019s Teacher Training University, 144\/8 Gogol Street, Almaty 050000, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anipa","family":"Tapalova","sequence":"additional","affiliation":[{"name":"Laboratory of Engineering Profile \u201cPhysical and Chemical Methods of Analysis\u201d, Korkyt Ata Kyzylorda University, 29A, Aiteke Bi Street, Kyzylorda 120014, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8765-3386","authenticated-orcid":false,"given":"Nurbol","family":"Appazov","sequence":"additional","affiliation":[{"name":"Laboratory of Engineering Profile \u201cPhysical and Chemical Methods of Analysis\u201d, Korkyt Ata Kyzylorda University, 29A, Aiteke Bi Street, Kyzylorda 120014, Kazakhstan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2938-7352","authenticated-orcid":false,"given":"Alexander","family":"Burilov","sequence":"additional","affiliation":[{"name":"Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center, Russian Academy of Sciences, Akad. Arbuzov St. 8, Kazan 420088, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,18]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S1473-3099(25)00118-5","article-title":"The WHO Bacterial Priority Pathogens List 2024: A Prioritisation Study to Guide Research, Development, and Public Health Strategies against Antimicrobial Resistance","volume":"25","author":"Sati","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global Burden of Bacterial Antimicrobial Resistance 1990\u20132021: A Systematic Analysis with Forecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"280","DOI":"10.1038\/s41579-022-00820-y","article-title":"Molecular Mechanisms of Antibiotic Resistance Revisited","volume":"21","author":"Darby","year":"2023","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Munita, J.M., and Arias, C.A. (2016). Mechanisms of Antibiotic Resistance. Microbiol. Spectr., 4.","DOI":"10.1128\/microbiolspec.VMBF-0016-2015"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e202414325","DOI":"10.1002\/anie.202414325","article-title":"Fighting Antimicrobial Resistance: Innovative Drugs in Antibacterial Research","volume":"64","author":"Gao","year":"2025","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Chawla, M., Verma, J., Gupta, R., and Das, B. (2022). Antibiotic Potentiators Against Multidrug-Resistant Bacteria: Discovery, Development, and Clinical Relevance. Front. Microbiol., 13.","DOI":"10.3389\/fmicb.2022.887251"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1016\/j.cmet.2019.06.009","article-title":"Bacterial Metabolism and Antibiotic Efficacy","volume":"30","author":"Stokes","year":"2019","journal-title":"Cell Metab."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Li, H., Zhou, X., Huang, Y., Liao, B., Cheng, L., and Ren, B. (2021). Reactive Oxygen Species in Pathogen Clearance: The Killing Mechanisms, the Adaption Response, and the Side Effects. Front. Microbiol., 11, Erratum in Front. Microbiol.\u00a02021, 12, 685133. https:\/\/doi.org\/10.3389\/fmicb.2021.685133. PMID: 33613470; PMCID: PMC7889972.","DOI":"10.3389\/fmicb.2020.622534"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Alfei, S., Schito, G.C., Schito, A.M., and Zuccari, G. (2024). Reactive Oxygen Species (ROS)-Mediated Antibacterial Oxidative Therapies: Available Methods to Generate ROS and a Novel Option Proposal. Int. J. Mol. Sci., 25.","DOI":"10.20944\/preprints202405.1628.v1"},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Dagah, O.M.A., Silaa, B.B., Zhu, M., Pan, Q., Qi, L., Liu, X., Liu, Y., Peng, W., Ullah, Z., and Yudas, A.F. (2024). Exploring Immune Redox Modulation in Bacterial Infections: Insights into Thioredoxin-Mediated Interactions and Implications for Understanding Host\u2013Pathogen Dynamics. Antioxidants, 13.","DOI":"10.3390\/antiox13050545"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"4679","DOI":"10.1021\/acs.chemrev.3c00420","article-title":"Mechanisms of Biological Effects of Ionic Liquids: From Single Cells to Multicellular Organisms","volume":"124","author":"Egorova","year":"2024","journal-title":"Chem. Rev."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"108753","DOI":"10.1016\/j.cbi.2019.108753","article-title":"Delivery Nanosystems Based on Sterically Hindered Phenol Derivatives Containing a Quaternary Ammonium Moiety: Synthesis, Cholinesterase Inhibition and Antioxidant Activity","volume":"310","author":"Pashirova","year":"2019","journal-title":"Chem.-Biol. Interact."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1039\/C8MD00481A","article-title":"Design, Synthesis, and Biological Activity of Novel Ammonium Salts Containing Sterically Hindered Phenolic Fragment and Phosphoryl Group","volume":"9","author":"Starodubtseva","year":"2018","journal-title":"MedChemComm"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"234","DOI":"10.1016\/j.mencom.2023.02.027","article-title":"Synthesis of New P-Quinone Methide Containing Morpholine Fragment: Access to (Diarylmethyl)Phosphonamidates with Antitumor Activity","volume":"33","author":"Gibadullina","year":"2023","journal-title":"Mendeleev Commun."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"111735","DOI":"10.1016\/j.ejmech.2019.111735","article-title":"New 2,6-Diaminopyridines Containing a Sterically Hindered Benzylphosphonate Moiety in the Aromatic Core as Potential Antioxidant and Anti-Cancer Drugs","volume":"184","author":"Gibadullina","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Chugunova, E., Gibadullina, E., Matylitsky, K., Bazarbayev, B., Neganova, M., Volcho, K., Rogachev, A., Akylbekov, N., Nguyen, H.B.T., and Voloshina, A. (2023). Diverse Biological Activity of Benzofuroxan\/Sterically Hindered Phenols Hybrids. Pharmaceuticals, 16.","DOI":"10.3390\/ph16040499"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Gibadullina, E., Neganova, M., Aleksandrova, Y., Nguyen, H.B.T., Voloshina, A., Khrizanforov, M., Nguyen, T.T., Vinyukova, E., Volcho, K., and Tsypyshev, D. (2023). Hybrids of Sterically Hindered Phenols and Diaryl Ureas: Synthesis, Switch from Antioxidant Activity to ROS Generation and Induction of Apoptosis. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms241612637"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1111\/j.1745-4565.1984.tb00479.x","article-title":"The Antimicrobial Activity of Phenolic Antioxidants in Foods: A Review","volume":"6","author":"Raccach","year":"1984","journal-title":"J. Food Saf."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1108","DOI":"10.4315\/0362-028X-45.12.1108","article-title":"Effect of BHA, BHT and Potassium Sorbate on Growth of Staphylococcus Aureus in a Model System and Process Cheese","volume":"45","author":"Parada","year":"1982","journal-title":"J. Food Prot."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1128\/AAC.10.1.96","article-title":"Inactivation of the Enveloped Bacteriophage by Butylated Hydroxytoluene and Butylated Hydroxyanisole","volume":"10","author":"Paul","year":"1976","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1016\/j.chemosphere.2008.10.039","article-title":"Mechanisms of Cytotoxicity of 2- or 2,6-Di-Tert-Butylphenols and 2-Methoxyphenols in Terms of Inhibition Rate Constant and a Theoretical Parameter","volume":"74","author":"Kadoma","year":"2009","journal-title":"Chemosphere"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1016\/S0009-2797(02)00161-8","article-title":"Responses of Tumorigenic and Non-Tumorigenic Mouse Lung Epithelial Cell Lines to Electrophilic Metabolites of the Tumor Promoter Butylated Hydroxytoluene","volume":"145","author":"Sun","year":"2003","journal-title":"Chem. Biol. Interact."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1021\/tx800162p","article-title":"Carbonyl Reductase Inactivation May Contribute to Mouse Lung Tumor Promotion by Electrophilic Metabolites of Butylated Hydroxytoluene: Protein Alkylation in Vivo and in Vitro","volume":"21","author":"Shearn","year":"2008","journal-title":"Chem. Res. Toxicol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"13757","DOI":"10.1039\/D0NR04037A","article-title":"Bi-Functional Sterically Hindered Phenol Lipid-Based Delivery Systems as Potential Multi-Target Agents against Alzheimer\u2019s Disease via an Intranasal Route","volume":"12","author":"Burilova","year":"2020","journal-title":"Nanoscale"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Qureshi, A., Ouattara, L.A., El-Sayed, N.S., Verma, A., Doncel, G.F., Choudhary, M.I., Siddiqui, H., and Parang, K. (2022). Synthesis and Evaluation of Anti-HIV Activity of Mono- and Di-Substituted Phosphonamidate Conjugates of Tenofovir. Molecules, 27.","DOI":"10.3390\/molecules27144447"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2040206618775243","DOI":"10.1177\/2040206618775243","article-title":"Phosphoramidates and Phosphonamidates (ProTides) with Antiviral Activity","volume":"26","author":"Slusarczyk","year":"2018","journal-title":"Antivir. Chem. Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"8658","DOI":"10.1021\/acs.jmedchem.8b00655","article-title":"Phosphonamidate Prodrugs of a Butyrophilin Ligand Display Plasma Stability and Potent V\u03b39 V\u03b42 T Cell Stimulation","volume":"61","author":"Lentini","year":"2018","journal-title":"J. Med. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10400","DOI":"10.1021\/acs.jmedchem.6b00523","article-title":"Nucleoside Phosphate and Phosphonate Prodrug Clinical Candidates","volume":"59","author":"Thornton","year":"2016","journal-title":"J. Med. Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"100063","DOI":"10.1016\/j.medidd.2020.100063","article-title":"Development and Clinical Application of Phosphorus-Containing Drugs","volume":"8","author":"Yu","year":"2020","journal-title":"Med. Drug Discov."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2462","DOI":"10.1039\/D4MD00208C","article-title":"Phosphonodiamidate Prodrugs of Phosphoantigens (ProPAgens) Exhibit Potent V\u03b39\/V\u03b42 T Cell Activation and Eradication of Cancer Cells","volume":"15","author":"Xu","year":"2024","journal-title":"RSC Med. Chem."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Kre\u010dmerov\u00e1, M., Majer, P., Rais, R., and Slusher, B.S. (2022). Phosphonates and Phosphonate Prodrugs in Medicinal Chemistry: Past Successes and Future Prospects. Front. Chem., 10.","DOI":"10.3389\/fchem.2022.889737"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"15028","DOI":"10.1039\/D1SC04445A","article-title":"Rationalizing the Generation of Broad Spectrum Antibiotics with the Addition of a Positive Charge","volume":"12","author":"Haloi","year":"2021","journal-title":"Chem. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8382","DOI":"10.1021\/acs.jmedchem.3c00206","article-title":"Basic Nitrogen (BaN) Is a Key Property of Antimalarial Chemical Space","volume":"66","author":"Valluri","year":"2023","journal-title":"J. Med. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/nyas.13598","article-title":"The Challenge of Converting Gram-Positive-Only Compounds into Broad-Spectrum Antibiotics","volume":"1435","author":"Richter","year":"2019","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"394","DOI":"10.1021\/acsinfecdis.2c00469","article-title":"From Antibacterial to Antibiofilm Targeting: An Emerging Paradigm Shift in the Development of Quaternary Ammonium Compounds (QACs)","volume":"9","author":"Saverina","year":"2023","journal-title":"ACS Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Vereshchagin, A.N., Frolov, N.A., Egorova, K.S., Seitkalieva, M.M., and Ananikov, V.P. (2021). Quaternary Ammonium Compounds (QACs) and Ionic Liquids (ILs) as Biocides: From Simple Antiseptics to Tunable Antimicrobials. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22136793"},{"key":"ref_37","unstructured":"Schmidt, A., Brunetti, H., and Schwarzenbach, K. (1981). Process for the Manufacture of Benzylphosphonates. (DE2203837C3), Germany Patent."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e21366","DOI":"10.1002\/hc.21366","article-title":"Novel O-Alkyl (3,5-Di-tert-Butyl-4-Hydroxybenzyl)Phosphonochloridates: Synthesis and Properties","volume":"28","author":"Gibadullina","year":"2017","journal-title":"Heteroat. Chem."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Amerkhanova, S.K., Voloshina, A.D., Mirgorodskaya, A.B., Lyubina, A.P., Kuznetsova, D.A., Kushnazarova, R.A., Mikhailov, V.A., and Zakharova, L.Y. (2021). Antimicrobial Properties and Cytotoxic Effect of Imidazolium Geminis with Tunable Hydrophobicity. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222313148"},{"key":"ref_40","unstructured":"Clinical and Laboratory Standards Institute (CLSI) (2018). Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically, CLSI. [11th ed.]. CLSI Standard M07."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"6152","DOI":"10.1021\/acs.jmedchem.7b00380","article-title":"Semisynthetic Flavone-Derived Antimicrobials with Therapeutic Potential against Methicillin-Resistant Staphylococcus Aureus (MRSA)","volume":"60","author":"Lin","year":"2017","journal-title":"J. Med. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1128\/jb.156.2.837-845.1983","article-title":"Chemical Mechanism of the Gram Stain and Synthesis of a New Electron-Opaque Marker for Electron Microscopy Which Replaces the Iodine Mordant of the Stain","volume":"156","author":"Davies","year":"1983","journal-title":"J. Bacteriol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.mimet.2017.06.004","article-title":"Comparison of the XTT and Resazurin Assays for Quantification of the Metabolic Activity of Staphylococcus Aureus Biofilm","volume":"139","author":"Alonso","year":"2017","journal-title":"J. Microbiol. Methods"},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Wang, L., Nan, S., Wang, Q., Xu, Y., Cui, M., Wang, F., Liu, Y., Hou, G., Liu, Z., and Zhou, W. (2026). A Series of Quaternary Ammonium Salt Antibacterial Agents Synthesized and Prepared for Constructing and Screening Antibacterial Coatings with Biosafety on Polypropylene. Front. Microbiol., 17.","DOI":"10.3389\/fmicb.2026.1718331"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/j.1365-2672.2010.04912.x","article-title":"Antimicrobial Cationic Surfactant, Cetyltrimethylammonium Bromide, Induces Superoxide Stress in Escherichia coli Cells","volume":"110","author":"Nakata","year":"2011","journal-title":"J. Appl. Microbiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"4101","DOI":"10.1021\/jo951862z","article-title":"Equilibrium Acidities and Homolytic Bond Dissociation Enthalpies of the Acidic C\u2212H Bonds in P-(Para-substituted benzyl)triphenylphosphonium Cations and Related Cations","volume":"61","author":"Zhang","year":"1996","journal-title":"J. Org. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"174","DOI":"10.1038\/s41392-024-01866-5","article-title":"Bacterial Persisters: Molecular Mechanisms and Therapeutic Development","volume":"9","author":"Niu","year":"2024","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"101322","DOI":"10.1016\/j.drup.2025.101322","article-title":"Metabolite-Driven Reprogramming of Bacterial Persisters: Mechanisms and Therapeutic Opportunities for Overcoming Antibiotic Tolerance","volume":"84","author":"Song","year":"2026","journal-title":"Drug Resist. Updat."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Yamasaki, R., Kawano, A., Sakakura, T., Takatsuji, Y., Haruyama, T., Yoshioka, Y., and Ariyoshi, W. (2020). Reactive Oxygen Species Penetrate Persister Cell Membranes of Escherichia coli for Effective Cell Killing. Front. Cell. Infect. Microbiol., 10.","DOI":"10.3389\/fcimb.2020.00496"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Rapacka-Zdonczyk, A. (2025). Beyond Resistance: Tolerance and Resilience of Bacteria to Photodynamic and Oxidative Stress. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms26188908"},{"key":"ref_51","unstructured":"Sheldrick, G.M. (SHELXTL, 2000). SHELXTL, Structure Determination Software Suite."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1107\/S2053229614024218","article-title":"Crystal structure refinement with SHELXL","volume":"71","author":"Sheldrick","year":"2015","journal-title":"Acta Crystallogr. Sect. C Struct. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"11258","DOI":"10.1021\/acs.jmedchem.0c01232","article-title":"Aryloxy Diester Phosphonamidate Prodrugs of Phosphoantigens (ProPAgens) as Potent Activators of V\u03b39\/V\u03b42 T-Cell Immune Responses","volume":"63","author":"Kadri","year":"2020","journal-title":"J. Med. Chem."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1021\/jm401853a","article-title":"Application of ProTide Technology to Gemcitabine: A Successful Approach to Overcome the Key Cancer Resistance Mechanisms Leads to a New Agent (NUC-1031) in Clinical Development","volume":"57","author":"Slusarczyk","year":"2014","journal-title":"J. Med. Chem."},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Tyagi, P., Singh, M., Kumari, H., Kumari, A., and Mukhopadhyay, K. (2015). Bactericidal Activity of Curcumin I Is Associated with Damaging of Bacterial Membrane. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0121313"},{"key":"ref_56","unstructured":"(2025, November 12). DCFDA\/H2DCFDA\u2014Cellular ROS Assay Kit Protocol. Abcam 2026, ab113851. Available online: https:\/\/doc.abcam.com\/datasheets\/active\/ab113851\/en-us\/dcfda-h2dcfda-cellular-ros-assay-kit-ab113851.pdf."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4524\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,22]],"date-time":"2026-05-22T04:12:02Z","timestamp":1779423122000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/10\/4524"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,18]]},"references-count":56,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2026,5]]}},"alternative-id":["ijms27104524"],"URL":"https:\/\/doi.org\/10.3390\/ijms27104524","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,18]]}}}