{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:54:49Z","timestamp":1791438889108,"version":"4.3.3"},"reference-count":42,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T00:00:00Z","timestamp":1785801600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,8,14]]},"abstract":"<jats:p>\n                    Natural and synthetic protoflavonoids exhibit a wide range of anticancer activities, including strong antiproliferative, proapoptotic, and DNA damage response\u2010inhibitory activities; however, the surrounding chemical space has remained largely unexplored. In this study, we report the synthesis and biological evaluation of a focused compound library containing the\n                    <jats:italic>p<\/jats:italic>\n                    \u2010hydroxydienone pharmacophore of protoflavonoids. Eleven derivatives were synthesized and characterized from chalcone precursors, and their antiproliferative activity was evaluated in four human adherent gynecological cancer cell lines (MCF\u20107, MDA\u2010MB\u2010231, HeLa, and SiHa). The investigated compounds exhibited mild to strong activity, with several showing notable selectivity for triple\u2010negative MDA\u2010MB\u2010231 cells. Our findings suggest that the unexplored chemical space around protoflavonoids might encompass compounds with valuable bioactivity and warrant further research.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70400","type":"journal-article","created":{"date-parts":[[2026,8,5]],"date-time":"2026-08-05T02:24:09Z","timestamp":1785896649000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Exploring the Chemical Space Around Protoflavonoids: Synthesis and Antitumor Activity of Protochalcones"],"prefix":"10.1002","volume":"21","author":[{"given":"T\u00edmea","family":"Gonda","sequence":"first","affiliation":[{"name":"Institute of Pharmacognosy University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Korn\u00e9l","family":"Sz\u0151ri","sequence":"additional","affiliation":[{"name":"Institute of Pharmacognosy University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed Dhahir","family":"Latif","sequence":"additional","affiliation":[{"name":"Institute of Pharmacognosy University of Szeged  Szeged Hungary"},{"name":"Department of Pharmacodynamics and Biopharmacy University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"K\u00fasz","sequence":"additional","affiliation":[{"name":"Institute of Pharmacognosy University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00e1nos","family":"Solt\u00e9sz","sequence":"additional","affiliation":[{"name":"Institute of Pharmacognosy University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Istv\u00e1n","family":"Zupk\u00f3","sequence":"additional","affiliation":[{"name":"Department of Pharmacodynamics and Biopharmacy University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erzs\u00e9bet","family":"Merny\u00e1k","sequence":"additional","affiliation":[{"name":"Institute of Pharmacognosy University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Attila","family":"Hunyadi","sequence":"additional","affiliation":[{"name":"Institute of Pharmacognosy University of Szeged  Szeged Hungary"},{"name":"HUN\u2010REN SZTE Biologically Active Natural Products Research Group  Szeged Hungary"},{"name":"Interdisciplinary Centre for Natural Products University of Szeged  Szeged Hungary"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,4]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jnatprod.5b01055"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd4510"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.4c02736"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41573-020-00114-z"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/nsr\/nwac206"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajps.2017.08.004"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101-014-9387-8"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.apsb.2019.01.003"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/162750"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2025.1570385"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28104009"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphar.2024.1513422"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11101-013-9288-2"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10637-010-9497-0"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.canlet.2008.03.007"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-11-0921"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.107.135442"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm070363a"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2013.04.007"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2011.01.015"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6482"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.taap.2020.115129"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0023922"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.8b01994"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules16119331"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202300675"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.03.108"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms17020083"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules19022061"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules21050611"},{"key":"e_1_2_10_32_1","first-page":"2737","article-title":"Antitumour Properties of Acridone Alkaloids on a Murine Lymphoma Cell Line","volume":"28","author":"R\u00e9thy B.","year":"2008","journal-title":"Anticancer Research"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-13-63"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.3332\/ecancer.2015.526"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.2147\/ITT.S273327"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.3390\/biom10111537"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms25063521"},{"key":"e_1_2_10_38_1","first-page":"93","article-title":"Triple\u2010Negative Breast Cancer: Treatment Challenges and Solutions","volume":"8","author":"Collignon J.","year":"2016","journal-title":"Breast Cancer"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph17062078"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2024.1405491"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41523-022-00468-0"},{"key":"e_1_2_10_42_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.reactfunctpolym.2023.105593"},{"key":"e_1_2_10_43_1","doi-asserted-by":"publisher","DOI":"10.22159\/ajpcr.2016.v9i5.13676"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70400","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.70400","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70400","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T05:35:24Z","timestamp":1791437724000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.70400"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,4]]},"references-count":42,"journal-issue":{"issue":"15","published-print":{"date-parts":[[2026,8,14]]}},"alternative-id":["10.1002\/cmdc.70400"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.70400","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,4]]},"assertion":[{"value":"2026-04-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-07-04","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-08-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70400"}}