{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T14:07:38Z","timestamp":1790690858664,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T00:00:00Z","timestamp":1790208000000},"content-version":"vor","delay-in-days":23,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"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":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Lactoperoxidase (LPO, EC 1.11.1.7), a heme metalloenzyme central to innate antimicrobial defence and implicated in mammary carcinogenesis, remains an underexplored target for metal\u2010based inhibitors. We evaluated six cyclometalated iridium(III) complexes bearing 2,2\u2032\u2010bipyridine\u20104,4\u2032\u2010dicarboxamide ancillary ligands with varied N\u2010substituents as LPO inhibitors. Kinetic analysis using LPO purified from bovine milk revealed nanomolar inhibition (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20090.64\u20133.12\u2009nM;\n                    <jats:italic>K\u1d62\u2009<\/jats:italic>\n                    =\u20090.05\u2009\u00b1\u20090.01\u20135.36\u2009\u00b1\u20091.88\u2009nM), representing an approximately 10\n                    <jats:sup>7<\/jats:sup>\n                    \u2010fold potency advantage over the benchmark sulfonamide acetazolamide. Lineweaver\u2013Burk analysis showed substituent\u2010dependent inhibition: complexes 1, 2, and 4 were competitive, whereas 3, 5, and 6 were non\u2010competitive, indicating that peripheral steric features influence the inhibition mechanism. Density functional theory calculations showed smaller HOMO\u2013LUMO gaps and higher electrophilicity indices than acetazolamide, although no single descriptor predicted activity within the series. Molecular docking supported binding within the distal heme cavity, with representative interactions including \u03c0\u2013\u03c0 stacking and hydrogen bonding involving Gln\u2010105 and His\u2010109. All complexes reduced MDA\u2010MB\u2010231 cell viability; among those with reliably determined IC\n                    <jats:sub>50<\/jats:sub>\n                    values, complex 4 showed the greatest cytotoxicity (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200918.28\u2009\u00b5M). These findings identify amide\u2010linked Ir(III) complexes as highly potent LPO inhibitors with substituent\u2010dependent inhibition modes.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70346","type":"journal-article","created":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T18:43:28Z","timestamp":1790275408000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Steric Control of Competitive Versus Noncompetitive Lactoperoxidase Inhibition by Amide\u2010Linked Iridium(III) Complexes"],"prefix":"10.1002","volume":"359","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 Seyh Edebali University Bilecik T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4086-8459","authenticated-orcid":false,"given":"Fatma","family":"Sa\u011f\u0131r","sequence":"additional","affiliation":[{"name":"Science and Advanced Technologies Research Center (BILTAM) Istanbul Medeniyet University Istanbul T\u00fcrkiye"},{"name":"Department of Molecular Biology and Genetics Istanbul Medeniyet University Istanbul 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":"Science and Advanced Technologies Research Center (BILTAM) Istanbul Medeniyet University Istanbul T\u00fcrkiye"},{"name":"Department of Chemistry Istanbul Medeniyet University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"\u00c7i\u011fdem","family":"\u015eahin","sequence":"additional","affiliation":[{"name":"Department of Engineering Basic Sciences Istanbul Medeniyet University Istanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,24]]},"reference":[{"key":"e_1_2_9_2_1","first-page":"227","article-title":"Structure, Functions and Applications of Lactoperoxidase in Natural Antimicrobial Systems","volume":"50","author":"Wit J. 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