{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T06:48:36Z","timestamp":1790318916213,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T00:00:00Z","timestamp":1770076800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["analyticalsciencejournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Drug Development Research"],"published-print":{"date-parts":[[2026,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In this study, a series of novel iridium(III) complexes incorporating 2\u2010phenylimidazo[4,5\u2010f][1,10]phenanthroline ligands with different substituents (methyl (\n                    <jats:bold>1a<\/jats:bold>\n                    ), isopropyl (\n                    <jats:bold>2a<\/jats:bold>\n                    ), methoxy (\n                    <jats:bold>3a<\/jats:bold>\n                    ), phenyl (\n                    <jats:bold>4a<\/jats:bold>\n                    )) were evaluated for their\n                    <jats:italic>in vitro<\/jats:italic>\n                    inhibitory activities against anticholinesterase (acetylcholinesterase [AChE], butyrylcholinesterase [BChE]) and carbonic anhydrase [hCA I] and [hCA II]) enzymes. Among the tested compounds,\n                    <jats:bold>2a<\/jats:bold>\n                    demonstrated exceptional potency with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 66.5\u2009\u00b1\u20099.06\u2009nM for AChE and 26.45\u2009\u00b1\u20095.00\u2009nM for BChE, significantly outperforming tacrine. Compound\n                    <jats:bold>4a<\/jats:bold>\n                    also exhibited strong inhibition of hCA I (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200933.0\u2009\u00b1\u20097.09\u2009nM) and hCA II (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200941.79\u2009\u00b1\u20098.09\u2009nM), surpassing the reference drug acetazolamide. Molecular docking studies revealed that compound\n                    <jats:bold>4a<\/jats:bold>\n                    exhibited the strongest binding affinity with BChE (PDB: 4BDS) at \u201012.06\u2009kcal\/mol, while compound\n                    <jats:bold>2a<\/jats:bold>\n                    showed strong binding to hCA II (PDB: 3HS4) at \u20108.768\u2009kcal\/mol. Molecular dynamics simulations over 150 ns confirmed the structural stability of the protein\u2010ligand complexes. Cell viability assays showed that compounds\n                    <jats:bold>1a\u20134a<\/jats:bold>\n                    decreased PC3 prostate cancer cell viability in a concentration\u2010dependent manner, with IC\n                    <jats:sub>50<\/jats:sub>\n                    values of 10.09, 3.95, 11.39, and 4.51\u2009\u00b5M, respectively. This comprehensive study highlights iridium(III) complexes as multitarget therapeutic agents with potent anticholinesterase and carbonic anhydrase inhibitory properties, offering promise for treating neurodegenerative and metabolic disorders.\n                  <\/jats:p>","DOI":"10.1002\/ddr.70244","type":"journal-article","created":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T14:55:32Z","timestamp":1770130532000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Potent Multi\u2010Target Inhibition of Cholinesterases and Carbonic Anhydrases by Iridium(III)\u2013Phenanthroline Derivatives: Integrated Structure\u2013Activity Relationship, Molecular Docking and Anticancer Cell Culture Studies"],"prefix":"10.1002","volume":"87","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0869-8517","authenticated-orcid":false,"given":"Zeynep","family":"K\u00f6ksal","sequence":"first","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"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2917-8860","authenticated-orcid":false,"given":"Kevser K\u00fcbra","family":"K\u0131rbo\u011fa","sequence":"additional","affiliation":[{"name":"Department of Bioengineering Bilecik Seyh Edebali University Bilecik T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma","family":"Sa\u011f\u0131r","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Genetics 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":[[2026,2,3]]},"reference":[{"key":"e_1_2_12_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-020-00149-4"},{"key":"e_1_2_12_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph18111685"},{"key":"e_1_2_12_4_1","doi-asserted-by":"publisher","DOI":"10.1063\/1.454033"},{"key":"e_1_2_12_5_1","doi-asserted-by":"publisher","DOI":"10.1039\/d4md00837e"},{"key":"e_1_2_12_6_1","unstructured":"BIOVIA.2020. 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