{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:32:23Z","timestamp":1786689143952,"version":"build-2736575974"},"reference-count":101,"publisher":"Wiley","license":[{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,13]],"date-time":"2026-08-13T00:00:00Z","timestamp":1786579200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["iubmb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Biotech and App Biochem"],"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Enzymatic browning mediated by polyphenol oxidase (PPO) remains a persistent challenge in food preservation. We report the rational design, synthesis, and evaluation of nine coumarin\u2010sulfonamide hybrid inhibitors (DS1\u20109) featuring 6,7\u2010dihydroxy\u20102\u2010oxo\u20102H\u2010chromen\u20104\u2010yl cores linked to N\u2010substituted benzenesulfonamide scaffolds, confirmed by FT\u2010IR and\n                    <jats:sup>1<\/jats:sup>\n                    H\u2010NMR. Enzyme kinetics against\n                    <jats:italic>Agaricus bisporus<\/jats:italic>\n                    tyrosinase revealed competitive inhibition across the series, with\n                    <jats:italic>\n                      K\n                      <jats:sub>i<\/jats:sub>\n                    <\/jats:italic>\n                    values spanning 46\u2013775 uM. DFT calculations (B3LYP\/def2\u2010TZVP) characterized the electronic landscape, HOMO\u2010LUMO energies (\u22125.716 to \u22126.455\u00a0eV; \u22121.716 to \u22122.278\u00a0eV), electrophilicity indices (3.5\u20134.2\u00a0eV), and dipole moments (4.98\u201311.24 Debye), while C\u2010PCM solvation modeling, MEP mapping, and RDG analysis established that intramolecular hydrogen bonding (sign\n                    <jats:italic>\u03bb<\/jats:italic>\n                    <jats:sub>2<\/jats:sub>\n                    <jats:italic>\u03c1<\/jats:italic>\n                    \u2248 \u22120.025 to \u22120.035 a.u.) preorganizes binding\u2010competent conformations. Molecular docking against PPO3 (PDB: 2Y9X) yielded binding affinities of \u22127.66 to \u22128.99\u00a0kcal\/mol, substantially exceeding tropolone (\u22124.65\u00a0kcal\/mol). DS\u20107 (\n                    <jats:italic>N<\/jats:italic>\n                    \u20103,4\u2010dimethylisoxazol\u20105\u2010yl) emerged as the lead compound (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 103 \u00b1 5.64\u00a0\u00b5M;\n                    <jats:italic>\n                      K\n                      <jats:sub>i<\/jats:sub>\n                    <\/jats:italic>\n                    = 46 uM), its potency driven by hydrogen bonding with Glu322, His85, and Asn260 alongside \u03c0\u2013sigma\/\u03c0\u2013anion contacts. DS\u20101 (\n                    <jats:italic>N<\/jats:italic>\n                    \u2010thiazol\u20102\u2010yl; IC\n                    <jats:sub>50<\/jats:sub>\n                    = 99.7 \u00b1 0.91\u00a0\u00b5M;\n                    <jats:italic>\n                      K\n                      <jats:sub>i<\/jats:sub>\n                    <\/jats:italic>\n                    = 57 uM) achieved comparable inhibition through a distinctive \u03c0\u2013sulfur interaction with His85 and copper coordination. DS\u20106 (\n                    <jats:italic>N<\/jats:italic>\n                    \u2010ethyl\u2010\n                    <jats:italic>N<\/jats:italic>\n                    \u2010phenyl; IC\n                    <jats:sub>50<\/jats:sub>\n                    = 90.3 \u00b1 4.86\u00a0\u00b5M;\n                    <jats:italic>\n                      K\n                      <jats:sub>i<\/jats:sub>\n                    <\/jats:italic>\n                    = 129 uM) outperformed docking predictions via apparent induced\u2010fit binding involving dual copper \u03c0\u2013alkyl coordination. SAR analysis identified the 6,7\u2010dihydroxycoumarin core, Val283 \u03c0\u2013sigma anchoring, and lipophilic N\u2010substitution as non\u2010negotiable pharmacophoric elements, positioning DS\u20107, DS\u20101, and DS\u20106 for food preservation and biocatalytic applications.\n                  <\/jats:p>","DOI":"10.1002\/bab.70198","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T06:15:31Z","timestamp":1786688131000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Development of Coumarin\u2010Sulfonamide Derivatives as Versatile Polyphenol Oxidase Inhibitors With Favorable Physicochemical and Pharmacokinetic Profiles"],"prefix":"10.1002","author":[{"given":"\u015eeref","family":"Karadeniz","sequence":"first","affiliation":[{"name":"Scientific and Technological Research Application and Research Center D\u00fczce University  D\u00fczce T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmad Badreddin","family":"Musatat","sequence":"additional","affiliation":[{"name":"Faculty of Sciences, Department of Chemistry Sakarya University  Sakarya T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beste","family":"Karadeniz","sequence":"additional","affiliation":[{"name":"D\u00fczce University Coordination Office of Specialization in Environment and Health Technologies  D\u00fczce T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye\u015fim","family":"Kaya","sequence":"additional","affiliation":[{"name":"Faculty of Arts and Science, Department of Chemistry Kocaeli University  Kocaeli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mustafa O\u011fuzhan","family":"Kaya","sequence":"additional","affiliation":[{"name":"Faculty of Arts and Science, Department of Chemistry Kocaeli University  Kocaeli T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"O\u011fuzhan","family":"\u00d6zdemir","sequence":"additional","affiliation":[{"name":"Veterinary Science Department, Technical Sciences Vocational School Batman University  Batman T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Halil \u0130brahim","family":"U\u011fra\u015f","sequence":"additional","affiliation":[{"name":"Faculty of Engineering, Department of Chemical Engineering Istanbul Beykent University  Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00dcmit","family":"\u00c7akir","sequence":"additional","affiliation":[{"name":"Faculty of Arts and Science, Department of Chemistry Bal\u0131kesir University  Bal\u0131kesir T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,13]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.supflu.2007.07.014"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.18203\/2349\u20103291.ijcp20194768"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202200508"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics15112554"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1080\/00958972.2023.2208260"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.21608\/ejchem.2020.33860.2707"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.07.019"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2017.07.031"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/tx500267x"},{"key":"e_1_2_10_11_1","first-page":"1","volume-title":"Burger's Medicinal Chemistry and Drug Discovery","author":"Ghosh A. 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