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For these purposes, 18 novel thiosemicarbazone derivatives\n                    <jats:bold>4a\u2013r<\/jats:bold>\n                    were synthesized. Among them, compound\n                    <jats:bold>4p<\/jats:bold>\n                    exhibited the most promising anticancer effects against A549 cells, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 5.11\u2009\u00b5M and a selectivity index (SI) of 10.55, surpassing the reference drug sorafenib. Compound\n                    <jats:bold>4p<\/jats:bold>\n                    also demonstrated potent enzyme inhibitory activity, particularly against hCA I (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u2009104.26\u2009nM) and hCA II (IC\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u200995.18\u2009nM), outperforming acetazolamide. In anticancer assays, compound\n                    <jats:bold>4p<\/jats:bold>\n                    (SI\u2009=\u200910.55) was about twice as effective as sorafenib (SI\u2009=\u20095.34), and in enzyme inhibition, it showed ~1.5\u2010fold greater potency than acetazolamide. Molecular docking studies show strong binding interactions of\n                    <jats:bold>4p<\/jats:bold>\n                    with hCA I, hCA II, and BRAF, with favorable docking scores and stable protein\u2013ligand complexes confirmed by 100\u2010ns and 250\u2010ns triplicate random seed MD simulations. Additionally, pharmacokinetic predictions indicated excellent drug\u2010like properties for\n                    <jats:bold>4p<\/jats:bold>\n                    , including high permeability, oral absorption, and adherence to Lipinski's rule. These findings highlight compound\n                    <jats:bold>4p<\/jats:bold>\n                    as a promising candidate for an anticancer agent targeting key enzymes involved in lung cancer progression.\n                  <\/jats:p>","DOI":"10.1002\/ardp.70116","type":"journal-article","created":{"date-parts":[[2025,10,15]],"date-time":"2025-10-15T07:37:02Z","timestamp":1760513822000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Targeting Lung Cancer: Synthesis, Characterization, Enzyme Inhibition, and Antiproliferative Activity of 1\n                    <i>H<\/i>\n                    \u2010Benzo[\n                    <i>f<\/i>\n                    ]chromen\u20101\u2010One\u2010Thiosemicarbazones Supported by Molecular Docking"],"prefix":"10.1002","volume":"358","author":[{"given":"Shahid","family":"Raza","sequence":"first","affiliation":[{"name":"Institute of Chemical Sciences Bahauddin Zakariya 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T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salman F.","family":"Alamery","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, College of Science King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdallah M.","family":"Elgorban","sequence":"additional","affiliation":[{"name":"Center of Excellence in Biotechnology Research (CEBR) King Saud University Riyadh Saudi Arabia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Faiqa","family":"Noreen","sequence":"additional","affiliation":[{"name":"Institute of Chemical Sciences Bahauddin Zakariya University Multan Pakistan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mazhar","family":"Hussain","sequence":"additional","affiliation":[{"name":"Institute of Chemical Sciences Bahauddin Zakariya University Multan 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