{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T12:15:01Z","timestamp":1790079301991,"version":"4.0.1"},"reference-count":38,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T00:00:00Z","timestamp":1782345600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Biochem &amp;amp; Molecular Tox"],"published-print":{"date-parts":[[2026,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lactoperoxidase (LPO; EC 1.11.1.7) is a milk\u2010derived heme oxidoreductase that plays a central role in the innate antimicrobial defense of mammals by catalyzing the H\n                    <jats:sub>2<\/jats:sub>\n                    O\n                    <jats:sub>2<\/jats:sub>\n                    \u2010dependent oxidation of substrates such as thiocyanate. Beyond this physiological role, the selective inhibition of LPO has gained increasing attention in both mechanistic enzymology and therapeutic development, particularly in oxidative stress\u2010related contexts. In this study, three sulfonamide derivatives, naphthalene\u20102\u2010sulfonamide (Naphthalene\u20102\u2010SA), 2,5\u2010dichlorothiophene\u20103\u2010sulfonamide (2,5\u2010DCTSA), and 6\u2010aminopyridine\u20103\u2010sulfonamide (6\u2010APSA), were evaluated as bovine LPO inhibitors using a combined experimental and multi\u2010level computational approach. Bovine LPO was purified approximately 509\u2010fold from skimmed milk by affinity chromatography, with a final specific activity of 168 EU\/mg. Kinetic assays revealed that all three compounds behaved as competitive inhibitors, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 0.69, 1.19, and 11.95\u2009\u00b5M and\n                    <jats:italic>K\u1d62<\/jats:italic>\n                    values of 0.50, 2.50, and 4.71\u2009\u00b5M, respectively. Naphthalene\u20102\u2010SA emerged as the most potent inhibitor and consistently ranked highest across all computational analyses, including molecular docking (\u22128.54\u2009kcal\/mol), 100\u2009ns molecular dynamics simulations, and MM\u2010GBSA binding free energy calculations (\u221220.24\u2009kcal\/mol). DFT\u2010based reactivity descriptors (HOMO\u2013LUMO gap, chemical softness) followed the experimental potency trend, while ADMET profiling further confirmed favorable drug\u2010like properties for all three compounds. The convergence of experimental kinetics with multiple independent computational observables, namely docking, MD stability, MM\u2010GBSA energetics, and DFT reactivity, provides new mechanistic insights into sulfonamide\u2013LPO interactions and identifies Naphthalene\u20102\u2010SA as a promising lead scaffold for the rational design of next\u2010generation LPO inhibitors.\n                  <\/jats:p>","DOI":"10.1002\/jbt.70978","type":"journal-article","created":{"date-parts":[[2026,6,25]],"date-time":"2026-06-25T12:25:54Z","timestamp":1782390354000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sulfonamide Derivatives as Competitive Lactoperoxidase Inhibitors Through Integrated Experimental and Multi\u2010Level Computational Analysis"],"prefix":"10.1002","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2917-8860","authenticated-orcid":false,"given":"Kevser K\u00fcbra","family":"K\u0131rbo\u011fa","sequence":"first","affiliation":[{"name":"Faculty of Engineering, Department of Bioengineering Bilecik \u015eeyh Edebali University Bilecik T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u015e\u00fckran","family":"Acar","sequence":"additional","affiliation":[{"name":"Faculty of Engineering, Department of Bioengineering Bilecik \u015eeyh Edebali University Bilecik T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0869-8517","authenticated-orcid":false,"given":"Zeynep","family":"K\u00f6ksal","sequence":"additional","affiliation":[{"name":"Department of Chemistry Istanbul Medeniyet University Istanbul T\u00fcrkiye"},{"name":"Science and Advanced Technologies Research Center (BILTAM) Istanbul Medeniyet University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,25]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.70055"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms12051010"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnut.2022.828065"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2024.110155"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.fbio.2024.105485"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2020.1814416"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd2467"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.3389\/fchem.2023.1206380"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-007-7359-2_15"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.apha.2025.02.004"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.4310\/CIS.241021221101"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-69850-1"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00894-024-06189-4"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jpcb.5c04085"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24031815"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557521666210401091147"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsps.2023.101889"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules22060793"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(76)90527-3"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1038\/227680a0"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202400909"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1080\/01480545.2019.1600532"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(75)90169-2"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2007.12.012"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/jcc.20945"},{"key":"e_1_2_10_27_1","first-page":"123","article-title":"The Lactoperoxidase System of Bovine Milk","volume":"27","author":"Reiter B.","year":"1985","journal-title":"Immunology Series"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.22300"},{"issue":"8","key":"e_1_2_10_29_1","first-page":"808","article-title":"Antibacterial Property of Goat Milk Lactoperoxidase","volume":"36","author":"Jacob B. M.","year":"1998","journal-title":"Indian Journal of Experimental Biology"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.4315\/0362-028X-47.9.724"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1051\/lait:1991215"},{"key":"e_1_2_10_32_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0007114500002208"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tifs.2004.11.002"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1054\/drup.2000.0146"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/med.10025"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2014.12.054"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.1080\/13543776.2018.1487400"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbt.21819"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1080\/10826068.2016.1185732"}],"container-title":["Journal of Biochemical and Molecular Toxicology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70978","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/jbt.70978","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/jbt.70978","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T11:43:17Z","timestamp":1790077397000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/jbt.70978"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,25]]},"references-count":38,"journal-issue":{"issue":"7","published-print":{"date-parts":[[2026,7]]}},"alternative-id":["10.1002\/jbt.70978"],"URL":"https:\/\/doi.org\/10.1002\/jbt.70978","archive":["Portico"],"relation":{},"ISSN":["1095-6670","1099-0461"],"issn-type":[{"value":"1095-6670","type":"print"},{"value":"1099-0461","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,25]]},"assertion":[{"value":"2026-04-18","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-06-25","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70978"}}