{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T08:01:29Z","timestamp":1785484889431,"version":"3.56.0"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T00:00:00Z","timestamp":1764892800000},"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":["Chemistry &amp;amp; Biodiversity"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    In this study, we investigated the effects of aminated quinolinequinones (\n                    <jats:bold>AQQ6<\/jats:bold>\n                    \u2013\n                    <jats:bold>16<\/jats:bold>\n                    ) on cancer cell lines previously selected by the National Cancer Institute (NCI). Analysis of the NCI\u201060 screening data from the Developmental Therapeutics Program (DTP) of the NCI revealed that 11 AQQs exhibited significant growth inhibitory activity across multiple cancer cell lines and were subsequently advanced to the five\u2010dose assay. Most AQQs effectively suppressed the proliferation of all leukemia cell lines in the single\u2010dose and five\u2010dose assays. Encouraged by these findings, we further examined the cytotoxic effects of selected AQQs (\n                    <jats:bold>AQQ6<\/jats:bold>\n                    and\n                    <jats:bold>AQQ9<\/jats:bold>\n                    ) in three human cancer cell lines, including HCT\u2010116 (colon cancer), DU\u2010145 (prostate cancer), and MDA\u2010MB\u2010231 (breast cancer), as well as in a normal cell line (HUVEC). Among the tested compounds,\n                    <jats:bold>AQQ6<\/jats:bold>\n                    demonstrated the highest potency against DU\u2010145 cells, with an IC\n                    <jats:sub>50<\/jats:sub>\n                    value of 3.13\u00a0\u00b1\u00a00.15\u00a0\u00b5M. To gain mechanistic insights, the effects of\n                    <jats:bold>AQQ6<\/jats:bold>\n                    on apoptosis, cell cycle distribution, and oxidative stress were evaluated.\n                    <jats:bold>AQQ6<\/jats:bold>\n                    inhibited DU\u2010145 cell proliferation by inducing apoptosis\/necrosis, accompanied by G\n                    <jats:sub>0<\/jats:sub>\n                    \/G\n                    <jats:sub>1<\/jats:sub>\n                    phase cell cycle arrest. In metabolic stability assays using human liver microsomes,\n                    <jats:bold>AQQ6<\/jats:bold>\n                    exhibited relatively low intrinsic clearance (Cl\n                    <jats:sub>int<\/jats:sub>\n                    ) and an improved half\u2010life (\n                    <jats:italic>T<\/jats:italic>\n                    <jats:sub>1\/2<\/jats:sub>\n                    ) compared to verapamil. However, pharmacokinetic studies in rats indicated poor oral bioavailability (%F\u00a0=\u00a04.2), likely due to extensive hepatic metabolism in rat liver microsomes. Molecular dynamics simulations targeting MAPK8, the protein likely involved in\n                    <jats:bold>AQQ6<\/jats:bold>\n                    activity, were conducted to elucidate molecular\u2010level binding interactions.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202501594","type":"journal-article","created":{"date-parts":[[2025,12,5]],"date-time":"2025-12-05T16:39:43Z","timestamp":1764952783000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Aminated Quinolinequinones With EDG(s) as a Prostate Cancer Inhibitor: Mechanistic Insights and Pharmacokinetic Limitations"],"prefix":"10.1002","volume":"23","author":[{"given":"Ayse Tarbin","family":"Jannuzzi","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Toxicology, Faculty of Pharmacy \u0130stanbul University  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayse Mine","family":"Yilmaz","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, School of Medicine\/Genetic and Metabolic Diseases Research and Investigation Center Marmara University  \u0130stanbul T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4871-0453","authenticated-orcid":false,"given":"Abanish","family":"Biswas","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences &amp; Technology Birla Institute of Technology Mesra  Ranchi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Subodh","family":"Mondal","sequence":"additional","affiliation":[{"name":"Bioanalysis Eurofins Advinus Biopharma Services India Pvt. Ltd.  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vinay N.","family":"Basavanakatti","sequence":"additional","affiliation":[{"name":"Adgyl Lifesciences Private Limited  Bengaluru India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3988-6120","authenticated-orcid":false,"given":"Hatice","family":"Y\u0131ld\u0131r\u0131m","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Engineering Faculty Istanbul University\u2010Cerrahpasa  Avcilar T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mahmut","family":"Y\u0131ld\u0131z","sequence":"additional","affiliation":[{"name":"Department of Chemistry Gebze Technical University  Gebze T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nil\u00fcfer","family":"Bayrak","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Istanbul University  Fatih T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9724-4153","authenticated-orcid":false,"given":"Venkatesan","family":"Jayaprakash","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences &amp; Technology Birla Institute of Technology Mesra  Ranchi India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5698-1109","authenticated-orcid":false,"given":"Ama\u00e7 Fatih","family":"TuYuN","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Faculty of Science Istanbul University  Fatih T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,12,5]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1617636114"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159\u20108290.CD\u201021\u20101059"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20102952(02)01154\u20101"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010010\u20109235\u20102"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1208\/s12248\u2010009\u20109128\u2010x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-94-024-1713-5_9"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00423\u2010019\u201001850\u20106"},{"key":"e_1_2_9_9_1","volume-title":"Colorectal Cancer","author":"WHO","year":"2023"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.20408"},{"key":"e_1_2_9_11_1","unstructured":"WHO Global Cancer Observatory: Cancer Today World Health Organization."},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2023\/6530719"},{"key":"e_1_2_9_13_1","first-page":"311","article-title":"Breast Cancer Metastasis","volume":"9","author":"Scully O. 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