{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T16:00:42Z","timestamp":1785081642118,"version":"3.55.0"},"reference-count":37,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"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; Biodiversity"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Cytotoxic activity of a series of 3\u2032,4\u2032,5\u2032\u2010trimethoxychalcones (\n                    <jats:bold>1\u201325<\/jats:bold>\n                    ) was evaluated against multiple human cancer cell lines under uniform experimental conditions. The compounds were designed to bear simple substitutions on ring B to allow direct comparison of substitution effects. Most derivatives showed higher cytotoxic potency than the reference drug melphalan in the more responsive models. Several compounds exhibited submicromolar half\u2010maximal inhibitory concentration (IC\n                    <jats:sub>50<\/jats:sub>\n                    ) values (\n                    <jats:bold>7<\/jats:bold>\n                    ,\n                    <jats:bold>8<\/jats:bold>\n                    ,\n                    <jats:bold>12<\/jats:bold>\n                    ,\n                    <jats:bold>13<\/jats:bold>\n                    ,\n                    <jats:bold>14<\/jats:bold>\n                    ,\n                    <jats:bold>17<\/jats:bold>\n                    ,\n                    <jats:bold>18<\/jats:bold>\n                    ,\n                    <jats:bold>20<\/jats:bold>\n                    ,\n                    <jats:bold>23<\/jats:bold>\n                    ). Low\u2010nanomolar activity was also observed. Compounds\n                    <jats:bold>4<\/jats:bold>\n                    ,\n                    <jats:bold>5<\/jats:bold>\n                    ,\n                    <jats:bold>9<\/jats:bold>\n                    ,\n                    <jats:bold>10<\/jats:bold>\n                    ,\n                    <jats:bold>15<\/jats:bold>\n                    ,\n                    <jats:bold>16<\/jats:bold>\n                    , and\n                    <jats:bold>24<\/jats:bold>\n                    showed particularly high potency. However, cytotoxic responses were strongly cell\u2010line dependent. MCF\u20107 (estrogen receptor\u2013positive breast carcinoma) and SKW\u20103 (T\u2010cell leukemia) cells were highly sensitive, whereas MDA\u2010MB\u2010231 (triple\u2010negative breast carcinoma) and K\u2010562 (BCR\u2010ABL\u2013positive leukemia) cells were less responsive. In the doxorubicin\u2010resistant HL\u201060\/DOX (multidrug\u2010resistant promyelocytic leukemia) subline,\n                    <jats:bold>10<\/jats:bold>\n                    retained activity. Compound\n                    <jats:bold>16<\/jats:bold>\n                    showed a nine\u2010fold increase in potency relative to HL\u201060. Hierarchical clustering, principal component analysis (PCA), and descriptor\u2010based quantitative structure\u2013activity relationship (QSAR) revealed no transferable trends. Molecular docking showed moderate, non\u2010selective interactions with multiple targets. Similar binding to human serum albumin was observed. Overall, these findings support cell\u2010line\u2010resolved evaluation and context\u2010aware optimization in 3\u2032,4\u2032,5\u2032\u2010trimethoxychalcone\u2010based anticancer research.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.71336","type":"journal-article","created":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T04:51:07Z","timestamp":1778734267000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cytotoxic Profiling of 3\u2032,4\u2032,5\u2032\u2010Trimethoxychalcones Reveals Cell\u2010Line\u2010Dependent Cytotoxic Activity: An In Vitro and In Silico Study"],"prefix":"10.1002","volume":"23","author":[{"given":"Aleksandar Y.","family":"Mehandzhiyski","sequence":"first","affiliation":[{"name":"Laboratory of Organic Electronics Department of Science and Technology (ITN) Link\u00f6ping University  Norrk\u00f6ping Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdessamad","family":"Beraich","sequence":"additional","affiliation":[{"name":"Physical Chemistry of the Natural Resources and Processes, Department of Chemistry, Faculty of Sciences Mohamed First University  Oujda Morocco"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhivko","family":"Velkov","sequence":"additional","affiliation":[{"name":"Department of Chemistry South\u2010West University \u201cNeofit Rilski\u201d  Blagoevgrad Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maya","family":"Zaharieva","sequence":"additional","affiliation":[{"name":"Department of Infectious Microbiology The Stephan Angeloff Institute of Microbiology Bulgarian Academy of Sciences  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spiro","family":"Konstantinov","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Pharmacotherapy and Toxicology Medical University of Sofia, Faculty of Pharmacy  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Batovska","sequence":"additional","affiliation":[{"name":"Institute of Chemical Engineering Bulgarian Academy of Sciences  Sofia Bulgaria"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/157488410790410579"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.7b00020"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231911595"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28104009"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2009.10.022"},{"key":"e_1_2_11_7_1","first-page":"379","article-title":"MDR\u2010reversal Activity of Chalcones","volume":"22","author":"Ivanova A.","year":"2008","journal-title":"In Vivo"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/530780"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134572"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2020.127144"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.22146\/ijc.72790"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.07.027"},{"key":"e_1_2_11_13_1","first-page":"1091","article-title":"Quantitative Structure\u2013Cytotoxicity Relationship of Chalcones","volume":"37","author":"Sakagami H.","year":"2017","journal-title":"Astronomy & Astrophysics"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm901278z"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.02.037"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom11060894"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.06.097"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules26123737"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1080\/17518253.2022.2089061"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.medidd.2025.100230"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.5c02394"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/1871520610909030336"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2021.132001"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2006.08.012"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2008.05.010"},{"key":"e_1_2_11_26_1","first-page":"31","article-title":"Nitric Oxide\u2010Scavenging Activity of In Vitro Cultured Balkan Medicinal and Aromatic Plants","volume":"19","author":"Mehandzhiyski A. 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