{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,22]],"date-time":"2026-06-22T09:16:43Z","timestamp":1782119803890,"version":"3.54.5"},"reference-count":83,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T00:00:00Z","timestamp":1749772800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>The clinical utility of sulfonamide antibiotics is increasingly challenged by antimicrobial resistance and pharmacokinetic limitations. In this study, we synthesized five graphene oxide\u2013sulfonamide nanoconjugates (GO\u2013S1 to GO\u2013S5) via covalent functionalization, comprehensively characterized them by IR, Raman, SEM, EDS, etc., and evaluated their antimicrobial, antibiofilm, cytotoxic, apoptotic, hemolytic and gene expression-modulating effects. While the free sulfonamides (S1\u2013S5) exhibited superior antimicrobial activity in planktonic cultures (MICs as low as 19 \u03bcg\/mL), their GO-functionalized counterparts demonstrated enhanced antibiofilm efficacy, particularly against Pseudomonas aeruginosa (MBIC: 78\u2013312 \u03bcg\/mL). Cytotoxicity studies using CellTiter assays and Incucyte live-cell imaging revealed low toxicity for all compounds below 250 \u03bcg\/mL. Morphological and gene expression analyses indicated mild pro-apoptotic effects, predominantly via caspase-9 and caspase-7 activation, with minimal caspase-3 involvement. Hemolysis assays confirmed the improved blood compatibility of GO\u2013Sx conjugates compared to GO alone. Furthermore, qRT-PCR analysis showed that GO\u2013Sx modulated the expression of key xenobiotic metabolism genes (CYPs and NATs), highlighting potential pharmacokinetic implications. Among all tested formulations, GOS3, GOS4 and GOS5 emerged as the most promising candidates, balancing low cytotoxicity, high hemocompatibility and strong antibiofilm activity. These findings support the use of graphene oxide nanocarriers to enhance the therapeutic potential of sulfonamides, particularly in the context of biofilm-associated infections.<\/jats:p>","DOI":"10.3390\/molecules30122585","type":"journal-article","created":{"date-parts":[[2025,6,13]],"date-time":"2025-06-13T09:51:24Z","timestamp":1749808284000},"page":"2585","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Multifunctional Evaluation of Graphene Oxide\u2013Sulfonamide Nanoconjugates: Antimicrobial, Antibiofilm, Cytocompatibility and Xenobiotic Metabolism Gene Expression Insight"],"prefix":"10.3390","volume":"30","author":[{"given":"Irina","family":"Zarafu","sequence":"first","affiliation":[{"name":"Faculty of Chemistry, University of Bucharest, 90 Panduri, 050663 Bucharest, Romania"},{"name":"Research Institute of the University of Bucharest (ICUB), University of Bucharest, 060023 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irina","family":"Mu\u0219at","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Bucharest, 90 Panduri, 050663 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmen","family":"Limban","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7685-3291","authenticated-orcid":false,"given":"Diana C.","family":"Nu\u021b\u0103","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0200-0867","authenticated-orcid":false,"given":"Ioana Daniela","family":"Dulama","sequence":"additional","affiliation":[{"name":"Institute of Multidisciplinary Research for Science and Technology, Valahia University of Targoviste, 130004 Targoviste, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1208-7732","authenticated-orcid":false,"given":"Cristiana","family":"Radulescu","sequence":"additional","affiliation":[{"name":"Faculty of Sciences and Arts, Valahia University of Targoviste, 130004 Targoviste, Romania"},{"name":"Doctoral School Chemical Engineering and Biotechnology, National University of Science and Technology Politehnica of Bucharest, 060042 Bucharest, Romania"},{"name":"Academy of Romanian Scientists, 050044 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2183-7996","authenticated-orcid":false,"given":"Raluca Maria","family":"Stirbescu","sequence":"additional","affiliation":[{"name":"Institute of Multidisciplinary Research for Science and Technology, Valahia University of Targoviste, 130004 Targoviste, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnaud","family":"Tatibouet","sequence":"additional","affiliation":[{"name":"Institut de Chimie Organique et Analytique (ICOA), Universit\u00e9 d\u2019Orl\u00e9ans-CNRS FR 2708-UMR 7311, 45067 Orl\u00e9ans, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6098-1857","authenticated-orcid":false,"given":"Carmen M.","family":"Chifiriuc","sequence":"additional","affiliation":[{"name":"Research Institute of the University of Bucharest (ICUB), University of Bucharest, 060023 Bucharest, Romania"},{"name":"Faculty of Biology, University of Bucharest, 91-95 Spl. Independentei, 050095 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4045-079X","authenticated-orcid":false,"given":"Luminita","family":"Marutescu","sequence":"additional","affiliation":[{"name":"Research Institute of the University of Bucharest (ICUB), University of Bucharest, 060023 Bucharest, Romania"},{"name":"Faculty of Biology, University of Bucharest, 91-95 Spl. Independentei, 050095 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcela","family":"Popa","sequence":"additional","affiliation":[{"name":"Research Institute of the University of Bucharest (ICUB), University of Bucharest, 060023 Bucharest, Romania"},{"name":"Faculty of Biology, University of Bucharest, 91-95 Spl. Independentei, 050095 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laura D.","family":"Dragu","sequence":"additional","affiliation":[{"name":"\u015etefan S Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5839-5605","authenticated-orcid":false,"given":"Elena","family":"Radu","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy, \u201cCarol Davila\u201d University of Medicine and Pharmacy, 6 Traian Vuia, 020956 Bucharest, Romania"},{"name":"\u015etefan S Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ioana","family":"Nicolau","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Bucharest, 90 Panduri, 050663 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9031-338X","authenticated-orcid":false,"given":"Coralia","family":"Bleotu","sequence":"additional","affiliation":[{"name":"Research Institute of the University of Bucharest (ICUB), University of Bucharest, 060023 Bucharest, Romania"},{"name":"Academy of Romanian Scientists, 050044 Bucharest, Romania"},{"name":"Faculty of Biology, University of Bucharest, 91-95 Spl. Independentei, 050095 Bucharest, Romania"},{"name":"\u015etefan S Nicolau Institute of Virology, Romanian Academy, 030304 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2216-3842","authenticated-orcid":false,"given":"Petre","family":"Ionita","sequence":"additional","affiliation":[{"name":"Faculty of Chemistry, University of Bucharest, 90 Panduri, 050663 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Spisz, P., Chylewska, A., Krolicka, A., Ramotowska, S., Dabrowska, A., and Makowski, M. (2021). Stimulation of Sulfonamides Antibacterial Drugs Activity as a Result of Complexation with Ru(III): Physicochemical and Biological Study. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms222413482"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s12551-021-00795-9","article-title":"Sulfonamide drugs: Structure, antibacterial property, toxicity, and biophysical interactions","volume":"13","author":"Ovung","year":"2021","journal-title":"Biophys. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"113","DOI":"10.2147\/DHPS.S347522","article-title":"Clinical Manifestations and Genetic Influences in Sulfonamide-Induced Hypersensitivity","volume":"14","author":"Asyraf","year":"2022","journal-title":"Drug Healthc. Patient Saf."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1111\/j.1469-0691.2011.03613.x","article-title":"Contemporary unconventional clinical use of co-trimoxazole","volume":"18","author":"Goldberg","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e13452","DOI":"10.1111\/tid.13452","article-title":"Sulfonamides without trimethoprim in the treatment of Nocardia infections: A case report and literature review","volume":"23","author":"Root","year":"2021","journal-title":"Transpl Infect Dis."},{"key":"ref_6","unstructured":"(2025, May 01). Patient Education: Methicillin-Resistant Staphylococcus aureus (MRSA) (Beyond the Basics). Available online: https:\/\/www.uptodate.com\/contents\/4025."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"3279","DOI":"10.1128\/AAC.48.9.3279-3283.2004","article-title":"In vitro activity of caspofungin combined with sulfamethoxazole against clinical isolates of Aspergillus spp.","volume":"48","author":"Yekutiel","year":"2004","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Dideikin, A.T., and Vul\u2019, A.Y. (2019). Graphene Oxide and Derivatives: The Place in Graphene Family. Front. Phys., 6.","DOI":"10.3389\/fphy.2018.00149"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/j.envpol.2015.11.053","article-title":"Adsorption of sulfonamides on reduced graphene oxides as affected by pH and dissolved organic matter","volume":"210","author":"Liu","year":"2016","journal-title":"Environ. Poll."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Yao, Q., Fan, B., Xiong, Y., Jin, C., Sun, Q., and Sheng, C. (2017). 3D assembly based on 2D structure of Cellulose Nanofibril\/Graphene Oxide Hybrid Aerogel for Adsorptive Removal of Antibiotics in Water. Sci. Rep., 7.","DOI":"10.1038\/srep45914"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"36615","DOI":"10.1007\/s11356-018-3368-1","article-title":"Kinetic, equilibrium, and thermodynamic performance of sulfonamides adsorption onto graphene","volume":"25","author":"Zhuang","year":"2018","journal-title":"Environ. Sci. Poll. Res. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.jiec.2016.05.021","article-title":"Sulfanilamide and silver nanoparticles-loaded polyvinyl alcohol-chitosan composite electrospun nanofibers: Synthesis and evaluation on synergism in wound healing","volume":"39","author":"Ganesh","year":"2016","journal-title":"J. Ind. Eng. Chem."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"539","DOI":"10.2217\/fmb.16.2","article-title":"The potential role of trimethoprim-sulfamethoxazole in the treatment of drug-resistant tuberculosis","volume":"11","author":"Palomino","year":"2016","journal-title":"Future Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1851","DOI":"10.1503\/cmaj.111152","article-title":"Considerations when prescribing trimethoprim-sulfamethoxazole","volume":"183","author":"Ho","year":"2011","journal-title":"Can. Med. Assoc. J."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1111\/hiv.12402","article-title":"A systematic review and meta-analysis of the relative efficacy and safety of treatment regimens for HIV-associated cerebral toxoplasmosis: Is trimethoprim-sulfamethoxazole a real option?","volume":"18","author":"Hernandez","year":"2017","journal-title":"HIV Med."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Fernandez-Villa, D., Aguilar, M.R., and Rojo, L. (2019). Folic Acid Antagonists: Antimicrobial and Immunomodulating Mechanisms and Applications. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20204996"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/j.ijpharm.2017.04.047","article-title":"Polymer-free electrospun nanofibers from sulfobutyl ether(7)-beta-cyclodextrin (SBE(7)-beta-CD) inclusion complex with sulfisoxazole: Fast-dissolving and enhanced water-solubility of sulfisoxazole","volume":"531","author":"Yildiz","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1016\/j.colsurfb.2015.02.019","article-title":"Sulfisoxazole\/cyclodextrin inclusion complex incorporated in electrospun hydroxypropyl cellulose nanofibers as drug delivery system","volume":"128","author":"Aytac","year":"2015","journal-title":"Colloids Surf. B Biointerfaces"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"D1214","DOI":"10.1093\/nar\/gkv1031","article-title":"ChEBI in 2016: Improved services and an expanding collection of metabolites","volume":"44","author":"Hastings","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1016\/j.neuint.2005.12.007","article-title":"Sulfisoxazole, an endothelin receptor antagonist, protects retinal neurones from insults of ischemia\/reperfusion or lipopolysaccharide","volume":"48","author":"Syed","year":"2006","journal-title":"Neurochem. Int."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1387","DOI":"10.1038\/s41467-019-09387-4","article-title":"Sulfisoxazole inhibits the secretion of small extracellular vesicles by targeting the endothelin receptor A","volume":"10","author":"Im","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_22","unstructured":"National Center for Biotechnology Information (2025, March 19). PubChem Compound Summary for CID 5333, Sulfanilamide, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Sulfanilamide."},{"key":"ref_23","unstructured":"National Center for Biotechnology Information (2025, March 19). PubChem Compound Summary for CID 5329, Sulfamethoxazole, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Sulfamethoxazole."},{"key":"ref_24","unstructured":"Kemnic, T.R., and Coleman, M. (2022). Trimethoprim Sulfamethoxazole, StatPearls."},{"key":"ref_25","unstructured":"National Center for Biotechnology Information (2025, March 19). PubChem Compound Summary for CID 5340, Sulfathiazole, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Sulfathiazole."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1016\/j.hoc.2012.02.002","article-title":"The antifolates","volume":"26","author":"Visentin","year":"2012","journal-title":"Hematol. Oncol. Clin. North. Am."},{"key":"ref_27","unstructured":"National Center for Biotechnology Information (2025, March 19). PubChem Compound Summary for 5339, Sulfasalazine, Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/compound\/Sulfasalazine."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"10233","DOI":"10.1021\/acsomega.8b01283","article-title":"Simple Synthesis of Large Graphene Oxide Sheets via Electrochemical Method Coupled with Oxidation Process","volume":"3","author":"Kumar","year":"2018","journal-title":"ACS Omega"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"4806","DOI":"10.1021\/nn1006368","article-title":"Improved Synthesis of Graphene Oxide","volume":"4","author":"Marcano","year":"2010","journal-title":"ACS Nano"},{"key":"ref_30","first-page":"58","article-title":"Graphene Oxide Synthesized by Using Modified Hummers Approach","volume":"2","author":"Shahriary","year":"2014","journal-title":"Int. J. Renew. Energy Environ. Eng."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.matchemphys.2015.01.005","article-title":"Graphene oxide powders with different oxidation degree, prepared by synthesis variations of the Hummers method","volume":"153","year":"2015","journal-title":"Mater. Chem. Phys."},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"King, A.A.K., Davies, B.R., Noorbehesht, N., Newman, P., Church, T.L., Harris, A.T., Raza, J.M., and Minett, A.I. (2016). A New Raman Metric for the Characterisation of Graphene oxide and its Derivatives. Sci. Rep., 6.","DOI":"10.1038\/srep19491"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"4547","DOI":"10.1016\/j.jece.2017.08.047","article-title":"Development of Cysteine Amide Reduced Graphene Oxide (CARGO) Nano-Adsorbents for Enhanced Uranyl Ions Removal from Aqueous Medium","volume":"5","author":"Verma","year":"2017","journal-title":"J. Environ. Chem. Eng."},{"key":"ref_34","first-page":"527","article-title":"A New material for bipolar plates used in fuel cells","volume":"61","author":"Negrea","year":"2016","journal-title":"Rom. J. Phys."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"012021","DOI":"10.1088\/1757-899X\/196\/1\/012021","article-title":"Defect and Magnetic Properties of Reduced Graphene Oxide Prepared from Old Coconut Shell","volume":"196","author":"Kurniasari","year":"2017","journal-title":"IOP Conf. Ser. Mater. Sci. Eng."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1021\/ja01539a017","article-title":"Preparation of Graphitic Oxide","volume":"80","author":"Hummers","year":"1958","journal-title":"J. Am. Chem. Soc."},{"key":"ref_37","unstructured":"Jang, J.I. (2013). Raman Spectroscopy of Graphene and Related Materials. New Developments in Photon and Materials Research, NOVA Science Publishers, Inc."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.1016\/j.bbamcr.2012.07.003","article-title":"The molecular mechanism of apoptosis upon caspase-8 activation: Quantitative experimental validation of a mathematical model","volume":"1823","author":"Kominami","year":"2012","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"23996","DOI":"10.18632\/oncotarget.15098","article-title":"Caspase-9: Structure, mechanisms and clinical application","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Toplicanin, A., Toncev, L., Matovic Zaric, V., and Sokic Milutinovic, A. (2022). Autoimmune Hemolytic Anemia in Inflammatory Bowel Disease-Report of a Case and Review of the Literature. Life, 12.","DOI":"10.3390\/life12111784"},{"key":"ref_41","first-page":"1113","article-title":"Immune complex haemolytic anaemia associated with sulfasalazine","volume":"320","author":"Teplitsky","year":"2000","journal-title":"BMJ"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"377","DOI":"10.7326\/0003-4819-101-3-377","article-title":"Sulfasalazine. Pharmacology, clinical use, toxicity, and related new drug development","volume":"101","author":"Peppercorn","year":"1984","journal-title":"Ann. Intern. Med."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1825","DOI":"10.2165\/00003495-200565130-00008","article-title":"Sulfasalazine: A review of its use in the management of rheumatoid arthritis","volume":"65","author":"Plosker","year":"2005","journal-title":"Drugs"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1038\/343278a0","article-title":"Identification and isolation of a membrane protein necessary for leukotriene production","volume":"343","author":"Miller","year":"1990","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1016\/0016-5085(90)90329-Y","article-title":"Clinical evidence supporting the radical scavenger mechanism of 5-aminosalicylic acid","volume":"98","author":"Nielsen","year":"1990","journal-title":"Gastroenterology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1038\/nri3661","article-title":"Cytokines in inflammatory bowel disease","volume":"14","author":"Neurath","year":"2014","journal-title":"Nat. Rev. Immunol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"559","DOI":"10.1038\/s41577-024-01008-6","article-title":"Strategies for targeting cytokines in inflammatory bowel disease","volume":"24","author":"Neurath","year":"2024","journal-title":"Nat. Rev. Immunol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"399","DOI":"10.1016\/S0022-3565(25)24345-2","article-title":"5-Aminosalicylic acid abrogates T-cell proliferation by blocking interleukin-2 production in peripheral blood mononuclear cells","volume":"272","author":"Stevens","year":"1995","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1016\/0006-2952(87)90262-0","article-title":"Inhibition of neutrophil degranulation and superoxide production by sulfasalazine. Comparison with 5-aminosalicylic acid, sulfapyridine and olsalazine","volume":"36","author":"Neal","year":"1987","journal-title":"Biochem. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Jabri, T., Khan, N.A., Makhlouf, Z., Akbar, N., Gul, J., Shah, M.R., and Siddiqui, R. (2023). Antibacterial Properties of Ethacridine Lactate and Sulfmethoxazole Loaded Functionalized Graphene Oxide Nanocomposites. Antibiotics, 12.","DOI":"10.3390\/antibiotics12040755"},{"key":"ref_51","doi-asserted-by":"crossref","unstructured":"AbouAitah, K., Sabbagh, F., and Kim, B.S. (2023). Graphene Oxide Nanostructures as Nanoplatforms for Delivering Natural Therapeutic Agents: Applications in Cancer Treatment, Bacterial Infections, and Bone Regeneration Medicine. Nanomaterials, 13.","DOI":"10.3390\/nano13192666"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"e2201523","DOI":"10.1002\/adhm.202201523","article-title":"Graphene-Based Nanocomposites as Antibacterial, Antiviral and Antifungal Agents","volume":"12","author":"Edirisinghe","year":"2023","journal-title":"Adv. Healthc. Mater."},{"key":"ref_53","doi-asserted-by":"crossref","unstructured":"Mohammadi Tabar, M., Khaleghi, M., Bidram, E., Zarepour, A., and Zarrabi, A. (2022). Penicillin and Oxacillin Loaded on PEGylated-Graphene Oxide to Enhance the Activity of the Antibiotics against Methicillin-Resistant Staphylococcus aureus. Pharmaceutics, 14.","DOI":"10.3390\/pharmaceutics14102049"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Brentnall, M., Rodriguez-Menocal, L., De Guevara, R.L., Cepero, E., and Boise, L.H. (2013). Caspase-9, caspase-3 and caspase-7 have distinct roles during intrinsic apoptosis. BMC Cell Biol., 14.","DOI":"10.1186\/1471-2121-14-32"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/jcph.1535","article-title":"Role of Oxidative Stress in Hypersensitivity Reactions to Sulfonamides","volume":"60","author":"Elzagallaai","year":"2020","journal-title":"J. Clin. Pharmacol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1186\/s12989-016-0168-y","article-title":"Toxicity of graphene-family nanoparticles: A general review of the origins and mechanisms","volume":"13","author":"Ou","year":"2016","journal-title":"Part. Fibre Toxicol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1016\/j.jfda.2014.01.009","article-title":"Assessment of the toxic potential of graphene family nanomaterials","volume":"22","author":"Guo","year":"2014","journal-title":"J. Food Drug Anal."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Wadhwa, R., Aggarwal, T., Thapliyal, N., Kumar, A., Yadav, P., Kumari, V., Charan Reddy, B.S., Chandra, P., and Maurya, P.K. (2019). Red blood cells as an efficient in vitro model for evaluating the efficacy of metallic nanoparticles. 3 Biotech., 9.","DOI":"10.1007\/s13205-019-1807-4"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1111\/febs.14606","article-title":"Oxidative stress, eryptosis and anemia: A pivotal mechanistic nexus in systemic diseases","volume":"286","author":"Bissinger","year":"2019","journal-title":"FEBS J."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1007\/s10853-023-09163-2","article-title":"Drying of graphene oxide: Effects on red blood cells and protein corona formation","volume":"59","author":"Martins","year":"2024","journal-title":"J. Mater. Sci."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1557\/jmr.2017.388","article-title":"Understanding the hemotoxicity of graphene nanomaterials through their interactions with blood proteins cells","volume":"33","author":"Kenry","year":"2018","journal-title":"J. Mater. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1039\/C8NH00318A","article-title":"Graphene oxide touches blood: In vivo interactions of bio-coronated 2D materials","volume":"4","author":"Palmieri","year":"2019","journal-title":"Nanoscale Horiz."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/j.ijbiomac.2021.01.151","article-title":"Insights into graphene oxide interaction with human serum albumin in isolated state and in blood plasma","volume":"175","author":"Taneva","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"55290","DOI":"10.1039\/C4RA09613D","article-title":"Interaction of graphene oxide with human serum albumin and its mechanism","volume":"4","author":"Ding","year":"2014","journal-title":"RSC Adv."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"94","DOI":"10.3390\/jox11030007","article-title":"The Central Role of Cytochrome P450 in Xenobiotic Metabolism-A Brief Review on a Fascinating Enzyme Family","volume":"11","author":"Esteves","year":"2021","journal-title":"J. Xenobiot."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"2705","DOI":"10.1111\/bph.12598","article-title":"Arylamine N-acetyltransferases: From drug metabolism and pharmacogenetics to drug discovery","volume":"171","author":"Sim","year":"2014","journal-title":"Br. J. Pharmacol."},{"key":"ref_67","unstructured":"Phang-Lyn, S., and Llerena, V.A. (2022). Biochemistry, Biotransformation, StatPearls."},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Iacopetta, D., Ceramella, J., Catalano, A., Scali, E., Scumaci, D., Pellegrino, M., Aquaro, S., Saturnino, C., and Sinicropi, M.S. (2023). Impact of Cytochrome P450 Enzymes on the Phase I Metabolism of Drugs. Appl. Sci., 13.","DOI":"10.3390\/app13106045"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"91","DOI":"10.1016\/j.apsb.2019.11.016","article-title":"New insights of CYP1A in endogenous metabolism: A focus on single nucleotide polymorphisms and diseases","volume":"10","author":"Lu","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"169","DOI":"10.1016\/B978-0-12-398339-8.00005-7","article-title":"Arylamine N-acetyltransferases\u2014from drug metabolism and pharmacogenetics to identification of novel targets for pharmacological intervention","volume":"63","author":"Sim","year":"2012","journal-title":"Adv. Pharmacol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1016\/j.apmt.2018.07.005","article-title":"Investigation into the toxic effects of graphene nanopores on lung cancer cells and biological tissues","volume":"12","author":"Tabish","year":"2018","journal-title":"Appl. Mater. Today"},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Valdehita, A., Fernandez-Cruz, M.L., and Navas, J.M. (2023). The Potentiating Effect of Graphene Oxide on the Arylhydrocarbon Receptor (AhR)-Cytochrome P4501A (Cyp1A) System Activated by Benzo(k)fluoranthene (BkF) in Rainbow Trout Cell Line. Nanomaterials., 13.","DOI":"10.3390\/nano13182501"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1038\/s41565-022-01260-8","article-title":"Graphene oxide elicits microbiome-dependent type 2 immune responses via the aryl hydrocarbon receptor","volume":"18","author":"Peng","year":"2023","journal-title":"Nat. Nanotechnol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1155\/2007\/976804","article-title":"N-acetyltransferase 2 slow acetylator genotype associated with adverse effects of sulphasalazine in the treatment of inflammatory bowel disease","volume":"21","author":"Chen","year":"2007","journal-title":"Can. J. Gastroenterol."},{"key":"ref_75","first-page":"2492","article-title":"Adverse effects of sulfasalazine in patients with rheumatoid arthritis are associated with diplotype configuration at the N-acetyltransferase 2 gene","volume":"29","author":"Tanaka","year":"2002","journal-title":"J. Rheumatol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1277","DOI":"10.1016\/0006-2952(93)90280-A","article-title":"Role of polymorphic and monomorphic human arylamine N-acetyltransferases in determining sulfamethoxazole metabolism","volume":"45","author":"Cribb","year":"1993","journal-title":"Biochem. Pharmacol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1007\/s11051-020-04935-2","article-title":"A mixed organic functionalized silica-graphene oxide as advanced material for pollutant removal","volume":"22","author":"Avramescu","year":"2020","journal-title":"J. Nanopart Res."},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Zarafu, I., Turcu, I., Culita, D.C., Petrescu, S., Popa, M., Chifiriuc, M.C., Limban, C., Telehoiu, A., and Ionita, P. (2018). Antimicrobial Features of Organic Functionalized Graphene-Oxide with Selected Amines. Materials, 11.","DOI":"10.3390\/ma11091704"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Zarafu, I., Limban, C., Radulescu, C., Dulama, I.D., Nuta, D.C., Chirita, C., Chifiriuc, M.C., Badiceanu, C.D., Popa, M., and Bleotu, C. (2022). Novel Structures of Functionalized Graphene Oxide with Hydrazide: Characterization and Bioevaluation of Antimicrobial and Cytocompatibility Features. Coatings, 12.","DOI":"10.3390\/coatings12010045"},{"key":"ref_80","first-page":"158224","article-title":"Aminocoumarin Derivatives Grafted on Graphene Oxide\u2014New Antimicrobial Agents to Combat the Resistance of Mycobacterium Tuberculosis and Eskape Pathogens","volume":"369","author":"Popa","year":"2023","journal-title":"Appl. Surf. Sci."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/j.apsusc.2018.11.242","article-title":"Covalent coupling of tuberculostatic agents and graphene oxide: A promising approach for enhancing and extending their antimicrobial applications","volume":"471","author":"Tudose","year":"2021","journal-title":"Appl. Surf. Sci."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"7174","DOI":"10.3390\/molecules20047174","article-title":"Synthesis and antiplatelet activity of antithrombotic thiourea compounds: Biological and structure-activity relationship studies","volume":"20","author":"Lourenco","year":"2015","journal-title":"Molecules"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1655","DOI":"10.3390\/cimb45020107","article-title":"Molecular Aspects of Hypoxic Stress Effects in Chronic Ethanol Exposure of Neuronal Cells","volume":"45","author":"Stoica","year":"2023","journal-title":"Curr. Issues Mol. Biol."}],"container-title":["Molecules"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/12\/2585\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T17:51:35Z","timestamp":1760032295000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1420-3049\/30\/12\/2585"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,6,13]]},"references-count":83,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2025,6]]}},"alternative-id":["molecules30122585"],"URL":"https:\/\/doi.org\/10.3390\/molecules30122585","relation":{},"ISSN":["1420-3049"],"issn-type":[{"value":"1420-3049","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,6,13]]}}}