{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T18:31:18Z","timestamp":1790706678918,"version":"4.1.0"},"reference-count":76,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T00:00:00Z","timestamp":1773014400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Ovarian cancer remains one of the most lethal gynecological malignancies, mainly due to late-stage diagnosis and frequent chemoresistance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Purpose<\/jats:title>\n                    <jats:p>This study sought to develop 3D-QSAR models\u2014Comparative Molecular Field and Similarity Index Analysis (CoMFA and CoMSIA)\u2014to predict the antiproliferative activity of synthetic chalcone derivatives against A2780 ovarian cancer cells and to explore potential mechanisms of action through antioxidant response biomarkers.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Materials and Methods<\/jats:title>\n                    <jats:p>\n                      CoMFA and CoMSIA models were developed using a dataset of 64 chalcone derivatives and validated using q\n                      <jats:sup>2<\/jats:sup>\n                      , r\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>ncv<\/jats:sub>\n                      , and other statistical metrics. Twelve chalcones predicted as active were synthesized and characterized by FT-IR and NMR spectroscopy. Their antiproliferative effects were evaluated using MTT assays, complemented by clonogenic testing, intracellular glutathione quantification, and analysis of biomarkers, including nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), and NAD(P)H: quinone oxidoreductase 1 (NQO1). The most active compounds were further assessed in a cisplatin-resistant A2780 subline, with\n                      <jats:italic>N<\/jats:italic>\n                      -acetylcysteine (NAC) used to probe reactive oxygen species (ROS)-dependent mechanisms.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results and Discussion<\/jats:title>\n                    <jats:p>\n                      The CoMFA and CoMSIA models demonstrated strong predictive performance (q\n                      <jats:sup>2<\/jats:sup>\n                      = 0.763\/0.789; r\n                      <jats:sup>2<\/jats:sup>\n                      <jats:sub>ncv<\/jats:sub>\n                      = 0.963\/0.920). Contour maps highlighted steric and electrostatic features linked to enhanced antiproliferative activity. The twelve synthesized chalcones exhibited experimental pIC\n                      <jats:sub>50<\/jats:sub>\n                      values that strongly correlated with model predictions. Compounds\n                      <jats:bold>065<\/jats:bold>\n                      ,\n                      <jats:bold>066<\/jats:bold>\n                      , and\n                      <jats:bold>072<\/jats:bold>\n                      showed the highest potency, with compound\n                      <jats:bold>072<\/jats:bold>\n                      also reducing clonogenic survival. Active derivatives increased intracellular glutathione and upregulated HO-1 without activating canonical Nrf2 signaling. In cisplatin-resistant A2780 cells, compounds\n                      <jats:bold>072<\/jats:bold>\n                      and\n                      <jats:bold>074<\/jats:bold>\n                      displayed markedly higher potency (IC\n                      <jats:sub>50<\/jats:sub>\n                      = 6.50 and 10.22\u00a0\u03bcM) than cisplatin (93.4\u00a0\u03bcM). Their cytotoxicity was abrogated by NAC, indicating a ROS-dependent mode of action.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>CoMFA and CoMSIA models accurately predicted the activity of synthetic chalcones, and the biological findings identify these derivatives as promising candidates for the treatment of ovarian cancer, including chemoresistant forms.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphar.2026.1746658","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:46:40Z","timestamp":1773038800000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["3D-QSAR study for the development of chalcone-based inhibitors targeting ovarian cancer cells with experimental validation"],"prefix":"10.3389","volume":"17","author":[{"given":"Manuel","family":"Valenzuela-Valderrama","sequence":"first","affiliation":[{"name":"Laboratorio de Carcinog\u00e9nesis Molecular, Facultad de Medicina y Ciencias de la Salud, Universidad Central de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aranxa","family":"Varas","sequence":"additional","affiliation":[{"name":"Carrera de Tecnolog\u00eda M\u00e9dica, Facultad de Medicina y Ciencias de la Salud, Universidad Central de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariaignacia","family":"Rubilar","sequence":"additional","affiliation":[{"name":"Laboratorio de Carcinog\u00e9nesis Molecular, Facultad de Medicina y Ciencias de la Salud, Universidad Central de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Lorca","sequence":"additional","affiliation":[{"name":"Facultad de Ciencias de la Vida, Carrera de Qu\u00edmica y Farmacia, Universidad Vi\u00f1a del Mar","place":["Vi\u00f1a del Mar, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jaime","family":"Mella","sequence":"additional","affiliation":[{"name":"Instituto de Qu\u00edmica, Facultad de Ciencias, Universidad de Valpara\u00edso","place":["Valpara\u00edso, Chile"]},{"name":"Centro de Investigaci\u00f3n, Desarrollo e Innovaci\u00f3n de Productos Bioactivos (CInBIO), Universidad de Valpara\u00edso","place":["Valpara\u00edso, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Espinosa-Bustos","sequence":"additional","affiliation":[{"name":"Departamento de Farmacia, Facultad de Qu\u00edmica y de Farmacia, Pontificia Universidad Cat\u00f3lica de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marco","family":"Mellado","sequence":"additional","affiliation":[{"name":"Direcci\u00f3n de Investigaci\u00f3n, Universidad Bernardo O\u2019Higgins","place":["Santiago, Chile"]},{"name":"Centro de Investigaci\u00f3n en Ingenier\u00eda de Materiales, Universidad Central de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"Echeverr\u00eda","sequence":"additional","affiliation":[{"name":"Departamento de Ciencias del Ambiente, Facultad de Qu\u00edmica y Biolog\u00eda, Universidad de Santiago de Chile","place":["Santiago, Chile"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,3,9]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1570385","DOI":"10.3389\/fphar.2025.1570385","article-title":"Pharmacological potential of natural chalcones: a recent studies and future perspective","volume":"16","author":"Adhikari","year":"2025","journal-title":"Front. Pharmacol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1186\/s13321-015-0069-3","article-title":"Why is tanimoto index an appropriate choice for fingerprint-based similarity calculations?","volume":"7","author":"Bajusz","year":"2015","journal-title":"J. Cheminform."},{"key":"B3","doi-asserted-by":"publisher","first-page":"e103988","DOI":"10.1371\/journal.pone.0103988","article-title":"Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes","volume":"9","author":"Beaufort","year":"2014","journal-title":"PLoS One"},{"key":"B4","first-page":"127","article-title":"Tetrazolium dyes as tools in cell biology: new insights into their cellular reduction","volume-title":"Biotechnology annual review","author":"Berridge","year":"2005"},{"key":"B5","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.molcata.2005.08.039","article-title":"LiOH\u00b7H2O as a novel dual activation catalyst for highly efficient and easy synthesis of 1,3-diaryl-2-propenones by claisen\u2013schmidt condensation under mild conditions","volume":"244","author":"Bhagat","year":"2006","journal-title":"J. Mol. Catal. A Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"3318","DOI":"10.1002\/jhet.4047","article-title":"Synthesis and evaluation of novel 1,2,4\u2010triazolo\u2010[3,4\u2010b]\u20101,3,4\u2010thiadiazole tethered chalcone hybrids as potential anticancer agents","volume":"57","author":"Bujji","year":"2020","journal-title":"J. Heterocycl. Chem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"4387","DOI":"10.3390\/molecules27144387","article-title":"Cytotoxic effects on breast cancer cell lines of chalcones derived from a natural precursor and their molecular docking analysis","volume":"27","author":"Bustos","year":"2022","journal-title":"Molecules"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1439","DOI":"10.3390\/ijms24021439","article-title":"Antitumoral activity of Leptocarpha rivularis flower extracts against gastric cancer cells","volume":"24","author":"Carrasco","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B9","doi-asserted-by":"publisher","first-page":"982","DOI":"10.1002\/jcc.540100804","article-title":"Validation of the general purpose tripos 5.2 force field","volume":"10","author":"Clark","year":"1989","journal-title":"J. Comput. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"5959","DOI":"10.1021\/ja00226a005","article-title":"Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins","volume":"110","author":"Cramer","year":"1988","journal-title":"J. Am. Chem. Soc."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1038\/ncomms3126","article-title":"Evaluating cell lines as tumour models by comparison of genomic profiles","volume":"4","author":"Domcke","year":"2013","journal-title":"Nat. Commun."},{"key":"B12","doi-asserted-by":"publisher","first-page":"7698","DOI":"10.1016\/j.bmc.2009.09.039","article-title":"Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: synthesis and biological evaluation of antivascular activity","volume":"17","author":"Ducki","year":"2009","journal-title":"Bioorg. Med. Chem."},{"key":"B13","doi-asserted-by":"publisher","first-page":"27769","DOI":"10.1021\/acsomega.2c01779","article-title":"Synthesis of chalcones derivatives and their biological activities: a review","volume":"7","author":"Elkanzi","year":"2022","journal-title":"ACS Omega"},{"key":"B14","doi-asserted-by":"publisher","first-page":"111954","DOI":"10.1016\/j.ejmech.2019.111954","article-title":"Design, synthesis, and validation of novel nitrogen-based chalcone analogs against triple negative breast cancer","volume":"187","author":"Elkhalifa","year":"2020","journal-title":"Eur. J. Med. Chem."},{"key":"B15","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2020\/5268985","article-title":"3D-QSAR study of the chalcone derivatives as anticancer agents","volume":"2020","author":"ElMchichi","year":"2020","journal-title":"J. Chem."},{"key":"B16","doi-asserted-by":"publisher","first-page":"1869","DOI":"10.1038\/onc.2011.384","article-title":"Molecular mechanisms of cisplatin resistance","volume":"31","author":"Galluzzi","year":"2012","journal-title":"Oncogene"},{"key":"B17","doi-asserted-by":"publisher","first-page":"3070","DOI":"10.1073\/pnas.89.7.3070","article-title":"High resistance to cisplatin in human ovarian cancer cell lines is associated with marked increase of glutathione synthesis","volume":"89","author":"Godwin","year":"1992","journal-title":"Proc. Natl. Acad. Sci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1016\/S1093-3263(01)00123-1","article-title":"Beware of q2","volume":"20","author":"Golbraikh","year":"2002","journal-title":"J. Mol. Graph. Model."},{"key":"B19","doi-asserted-by":"publisher","first-page":"133558","DOI":"10.1016\/j.molstruc.2022.133558","article-title":"Assessment of chalcone-vanillin as a selective chemosensor of As(III) in aqueous solution","volume":"1266","author":"Gonz\u00e1lez-Vergara","year":"2022","journal-title":"J. Mol. Struct."},{"key":"B20","doi-asserted-by":"publisher","first-page":"112957","DOI":"10.1016\/j.ejmech.2020.112957","article-title":"Chemistry, biosynthesis and biological activity of terpenoids and meroterpenoids in bacteria and fungi isolated from different marine habitats","volume":"210","author":"Gozari","year":"2021","journal-title":"Eur. J. Med. Chem."},{"key":"B21","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1002\/qsar.200610151","article-title":"Principles of QSAR models validation: internal and external","volume":"26","author":"Gramatica","year":"2007","journal-title":"QSAR Comb. Sci."},{"key":"B22","doi-asserted-by":"publisher","first-page":"1581","DOI":"10.1007\/s11696-020-01414-9","article-title":"C3 amino-substituted chalcone derivative with selective adenosine rA1 receptor affinity in the micromolar range","volume":"75","author":"Janse van Rensburg","year":"2021","journal-title":"Chem. Pap."},{"key":"B23","doi-asserted-by":"publisher","first-page":"953","DOI":"10.5012\/bkcs.2012.33.3.953","article-title":"Synthesis of biologically active chalcones and their anti-inflammatory effects","volume":"33","author":"Jeon","year":"2012","journal-title":"Bull. Korean Chem. Soc."},{"key":"B24","doi-asserted-by":"publisher","first-page":"3586","DOI":"10.1021\/acs.joc.5b00267","article-title":"Iron-facilitated oxidative radical decarboxylative cross-coupling between \u03b1-Oxocarboxylic acids and acrylic acids: an approach to \u03b1,\u03b2-Unsaturated carbonyls","volume":"80","author":"Jiang","year":"2015","journal-title":"J. Org. Chem."},{"key":"B25","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1186\/s13046-019-1351-4","article-title":"Cardamonin inhibits breast cancer growth by repressing HIF-1\u03b1-dependent metabolic reprogramming","volume":"38","author":"Jin","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B26","doi-asserted-by":"publisher","first-page":"1335","DOI":"10.3390\/nu15061335","article-title":"Cardamonin as a p38 MAPK signaling pathway activator inhibits human coronavirus OC43 infection in human lung cells","volume":"15","author":"Jin","year":"2023","journal-title":"Nutrients"},{"key":"B27","doi-asserted-by":"publisher","first-page":"4332","DOI":"10.3390\/molecules26144332","article-title":"Reaction of chalcones with cellular thiols. The effect of the 4-Substitution of chalcones and protonation state of the thiols on the addition process. Diastereoselective thiol addition","volume":"26","author":"Kenari","year":"2021","journal-title":"Molecules"},{"key":"B28","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1007\/s001090000084","article-title":"Recent developments in structure-based drug design","volume":"78","author":"Klebe","year":"2000","journal-title":"J. Mol. Med."},{"key":"B29","doi-asserted-by":"publisher","first-page":"4130","DOI":"10.1021\/jm00050a010","article-title":"Molecular similarity indices in a comparative analysis (CoMSIA) of drug molecules to correlate and predict their biological activity","volume":"37","author":"Klebe","year":"1994","journal-title":"J. Med. Chem."},{"key":"B30","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/j.phymed.2015.07.006","article-title":"Cytotoxicity of three naturally occurring flavonoid derived compounds (artocarpesin, cycloartocarpesin and isobavachalcone) towards multi-factorial drug-resistant cancer cells","volume":"22","author":"Kuete","year":"2015","journal-title":"Phytomedicine"},{"key":"B31","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.molcata.2007.05.016","article-title":"Zirconium chloride catalyzed efficient synthesis of 1,3-diaryl-2-propenones in solvent free conditions via aldol condensation","volume":"274","author":"Kumar","year":"2007","journal-title":"J. Mol. Catal. A Chem."},{"key":"B32","doi-asserted-by":"publisher","first-page":"3407","DOI":"10.2174\/0929867322666150729114829","article-title":"Chalcones as promising lead compounds on cancer therapy","volume":"22","author":"Leon-Gonzalez","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"B33","doi-asserted-by":"publisher","first-page":"379","DOI":"10.3892\/ol.2019.11069","article-title":"Activity and mechanism of flavokawain A in inhibiting permeability-glycoprotein expression in paclitaxel resistance of lung cancer","volume":"19","author":"Li","year":"2019","journal-title":"Oncol. Lett."},{"key":"B34","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1080\/14756366.2021.1976772","article-title":"A review on synthetic chalcone derivatives as tubulin polymerisation inhibitors","volume":"37","author":"Liu","year":"2022","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"889","DOI":"10.3390\/ph17070889","article-title":"2D\/3D-QSAR model development based on a quinoline pharmacophoric core for the inhibition of plasmodium falciparum: an in silico approach with experimental validation","volume":"17","author":"Lorca","year":"2024","journal-title":"Pharmaceuticals"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e202300042","DOI":"10.1002\/slct.202300042","article-title":"QSAR\u2010Guided study for the microwave\u2010assisted synthesis of 4\u2010Methylquinoline derivatives with antimycobacterial activity","volume":"8","author":"Luczywo","year":"2023","journal-title":"ChemistrySelect"},{"key":"B37","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1007\/s00894-021-04673-9","article-title":"A new isostructural halogenated chalcone with optical properties","volume":"27","author":"Ludovico","year":"2021","journal-title":"J. Mol. Model."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1095","DOI":"10.2147\/OTT.S155425","article-title":"First-line treatment of women with advanced ovarian cancer: focus on bevacizumab","volume":"12","author":"Marchetti","year":"2019","journal-title":"Onco. Targets. Ther."},{"key":"B39","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1007\/s00044-018-2245-2","article-title":"Synthesis of chalcones with antiproliferative activity on the SH-SY5Y neuroblastoma cell line: quantitative structure\u2013activity relationship models","volume":"27","author":"Mellado","year":"2018","journal-title":"Med. Chem. Res."},{"key":"B40","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1007\/s11030-019-09967-y","article-title":"Design, synthesis, antifungal activity, and structure\u2013activity relationship studies of chalcones and hybrid dihydrochromane\u2013chalcones","volume":"24","author":"Mellado","year":"2020","journal-title":"Mol. Divers."},{"key":"B41","doi-asserted-by":"publisher","first-page":"104689","DOI":"10.1016\/j.bioorg.2021.104689","article-title":"Combined 3D-QSAR and docking analysis for the design and synthesis of chalcones as potent and selective monoamine oxidase B inhibitors","volume":"108","author":"Mellado","year":"2021","journal-title":"Bioorg. Chem."},{"key":"B42","doi-asserted-by":"publisher","first-page":"4404","DOI":"10.1080\/14786419.2021.1984465","article-title":"Inhibition of Caco-2 and MCF-7 cancer cells using chalcones: synthesis, biological evaluation and computational study","volume":"36","author":"Mellado","year":"2022","journal-title":"Nat. Prod. Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"503","DOI":"10.3390\/pharmaceutics14030503","article-title":"Programmed cell death alterations mediated by synthetic indole chalcone resulted in cell cycle arrest, DNA damage, apoptosis and signaling pathway modulations in breast cancer model","volume":"14","author":"Michalkova","year":"2022","journal-title":"Pharmaceutics"},{"key":"B44","doi-asserted-by":"publisher","first-page":"10354","DOI":"10.3390\/ijms241210354","article-title":"Anticancer potential of natural chalcones: in vitro and in vivo evidence","volume":"24","author":"Michalkova","year":"2023","journal-title":"Int. J. Mol. Sci."},{"key":"B45","doi-asserted-by":"publisher","first-page":"127310","DOI":"10.1016\/j.molstruc.2019.127310","article-title":"Synthesis, structure-activity relationship and molecular docking studies of novel quinoline-chalcone hybrids as potential anticancer agents and tubulin inhibitors","volume":"1202","author":"Mirzaei","year":"2020","journal-title":"J. Mol. Struct."},{"key":"B46","doi-asserted-by":"publisher","first-page":"287","DOI":"10.2147\/IJWH.S197604","article-title":"Ovarian cancer in the world: epidemiology and risk factors","volume":"11","author":"Momenimovahed","year":"2019","journal-title":"Int. J. Womens. Health"},{"key":"B47","doi-asserted-by":"publisher","first-page":"3177","DOI":"10.1016\/j.tetlet.2007.03.054","article-title":"A simple and highly efficient method for the synthesis of chalcones by using borontrifluoride-etherate","volume":"48","author":"Narender","year":"2007","journal-title":"Tetrahedron Lett."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1878","DOI":"10.1248\/bpb.30.1878","article-title":"Isobavachalcone, a chalcone constituent of Angelica keiskei, induces apoptosis in neuroblastoma","volume":"30","author":"Nishimura","year":"2007","journal-title":"Biol. Pharm. Bull."},{"key":"B49","first-page":"71","volume-title":"Infrared spectroscopy: fundamentals and applications","year":"2004"},{"key":"B50","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s12982-024-00229-3","article-title":"A review of the current trends in computational approaches in drug design and metabolism","volume":"21","author":"Ouma","year":"2024","journal-title":"Discov. Public Heal."},{"key":"B51","article-title":"No title","year":"2025","journal-title":"World Cancer Res. Fund"},{"key":"B52","doi-asserted-by":"publisher","first-page":"5818","DOI":"10.1016\/j.bmcl.2010.07.128","article-title":"Fluorinated 2\u2032-hydroxychalcones as garcinol analogs with enhanced antioxidant and anticancer activities","volume":"20","author":"Padhye","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"B53","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1007\/s00044-024-03195-2","article-title":"Synthesis, characterization, and anticancer activity of syringaldehyde-derived chalcones against female cancers","volume":"33","author":"Pan","year":"2024","journal-title":"Med. Chem. Res."},{"key":"B54","doi-asserted-by":"publisher","first-page":"4362","DOI":"10.3390\/molecules25194362","article-title":"Chalcone methoxy derivatives exhibit antiproliferative and proapoptotic activity on canine lymphoma and leukemia cells","volume":"25","author":"Pawlak","year":"2020","journal-title":"Molecules"},{"key":"B55","doi-asserted-by":"publisher","first-page":"e106206","DOI":"10.1371\/journal.pone.0106206","article-title":"Tetramethoxychalcone, a chalcone derivative, suppresses proliferation, blocks cell cycle progression, and induces apoptosis of human ovarian cancer cells","volume":"9","author":"Qi","year":"2014","journal-title":"PLoS One"},{"key":"B56","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1038\/nrd2468","article-title":"Prodrugs: design and clinical applications","volume":"7","author":"Rautio","year":"2008","journal-title":"Nat. Rev. Drug Discov."},{"key":"B57","doi-asserted-by":"publisher","first-page":"1871","DOI":"10.1007\/s00044-017-1891-0","article-title":"Synthesis and biological evaluation of \u03b1-methyl-chalcone for anti-cervical cancer activity","volume":"26","author":"Ren","year":"2017","journal-title":"Med. Chem. Res."},{"key":"B58","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.ccell.2018.03.022","article-title":"NRF2 and the hallmarks of cancer","volume":"34","author":"Rojo de la Vega","year":"2018","journal-title":"Cancer Cell"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1071","DOI":"10.1002\/jcc.23231","article-title":"Some case studies on application of \u201c r m 2 \u201d metrics for judging quality of quantitative structure\u2013activity relationship predictions: emphasis on scaling of response data","volume":"34","author":"Roy","year":"2013","journal-title":"J. Comput. Chem."},{"key":"B60","doi-asserted-by":"publisher","first-page":"7177","DOI":"10.3390\/molecules26237177","article-title":"Chalcone scaffolds, bioprecursors of flavonoids: chemistry, bioactivities, and pharmacokinetics","volume":"26","author":"Rudrapal","year":"2021","journal-title":"Molecules"},{"key":"B61","doi-asserted-by":"publisher","first-page":"7541","DOI":"10.3390\/ijms25147541","article-title":"The induction of G2\/M phase cell cycle arrest and apoptosis by the chalcone derivative 1C in sensitive and resistant ovarian cancer cells is associated with ROS generation","volume":"25","author":"Salanci","year":"2024","journal-title":"Int. J. Mol. Sci."},{"key":"B62","doi-asserted-by":"publisher","first-page":"1809","DOI":"10.1016\/j.bmc.2014.01.058","article-title":"Polyphenols bearing cinnamaldehyde scaffold showing cell growth inhibitory effects on the cisplatin-resistant A2780\/Cis ovarian cancer cells","volume":"22","author":"Shin","year":"2014","journal-title":"Bioorg. Med. Chem."},{"key":"B63","doi-asserted-by":"publisher","first-page":"281","DOI":"10.17344\/acsi.2021.7080","article-title":"(E)-1-(4-Hydroxyphenyl)-3-(substituted-phenyl) prop-2-en-1-ones: synthesis, in vitro cytotoxic activity and molecular docking studies","volume":"69","author":"Sirka","year":"2022","journal-title":"Acta Chim. Slov."},{"key":"B64","doi-asserted-by":"publisher","first-page":"334","DOI":"10.1124\/pr.112.007336","article-title":"Computational methods in drug discovery","volume":"66","author":"Sliwoski","year":"2014","journal-title":"Pharmacol. Rev."},{"key":"B65","doi-asserted-by":"publisher","first-page":"129851","DOI":"10.1016\/j.molstruc.2020.129851","article-title":"Design, synthesis, anticancer evaluation and molecular docking studies of chalcone linked pyrido[4,3-b]pyrazin-5(6H)-one derivatives","volume":"1229","author":"Srilaxmi","year":"2021","journal-title":"J. Mol. Struct."},{"key":"B66","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.cbi.2018.07.005","article-title":"New chalcone derivative exhibits antiproliferative potential by inducing G2\/M cell cycle arrest, mitochondrial-mediated apoptosis and modulation of MAPK signalling pathway","volume":"292","author":"Takac","year":"2018","journal-title":"Chem. Biol. Interact."},{"key":"B67","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2013\/972913","article-title":"Role of glutathione in cancer progression and chemoresistance","volume":"2013","author":"Traverso","year":"2013","journal-title":"Oxid. Med. Cell. Longev."},{"key":"B68","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1002\/minf.201000061","article-title":"Best practices for QSAR model development, validation, and exploitation","volume":"29","author":"Tropsha","year":"2010","journal-title":"Mol. Inf."},{"key":"B69","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1021\/ci400004e","article-title":"X-ray crystallographic structures as a source of ligand alignment in 3D-QSAR","volume":"53","author":"Urnia\u017c","year":"2013","journal-title":"J. Chem. Inf. Model."},{"key":"B70","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1038\/bjc.2014.380","article-title":"Retinoic acid synergizes ATO-Mediated cytotoxicity by precluding Nrf2 activity in AML cells","volume":"111","author":"Valenzuela","year":"2014","journal-title":"Br. J. Cancer"},{"key":"B71","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1186\/s12943-024-01967-3","article-title":"Drug resistance in ovarian cancer: from mechanism to clinical trial","volume":"23","author":"Wang","year":"2024","journal-title":"Mol. Cancer"},{"key":"B72","doi-asserted-by":"publisher","first-page":"331","DOI":"10.1007\/s10822-016-9909-0","article-title":"Alignment-independent technique for 3D QSAR analysis","volume":"30","author":"Wilkes","year":"2016","journal-title":"J. Comput. Aided. Mol. Des."},{"key":"B73","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1080\/14756366.2016.1221825","article-title":"Synthesis and bioactivities of halogen bearing phenolic chalcones and their corresponding bis mannich bases","volume":"31","author":"Yamali","year":"2016","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"B74","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1007\/s12272-023-01481-y","article-title":"Arsenic trioxide: applications, mechanisms of action, toxicity and rescue strategies to date","volume":"47","author":"Yan","year":"2024","journal-title":"Arch. Pharm. Res."},{"key":"B75","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1038\/s41573-025-01145-0","article-title":"Thirty years of NRF2: advances and therapeutic challenges","volume":"24","author":"Zhang","year":"2025","journal-title":"Nat. Rev. Drug Discov."},{"key":"B76","doi-asserted-by":"publisher","first-page":"77","DOI":"10.1016\/j.taap.2016.08.023","article-title":"A new brominated chalcone derivative suppresses the growth of gastric cancer cells in vitro and in vivo involving ROS mediated up-regulation of DR5 and 4 expression and apoptosis","volume":"309","author":"Zhang","year":"2016","journal-title":"Toxicol. Appl. Pharmacol."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1746658\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T06:46:41Z","timestamp":1773038801000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2026.1746658\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,9]]},"references-count":76,"alternative-id":["10.3389\/fphar.2026.1746658"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2026.1746658","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,9]]},"article-number":"1746658"}}