{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:54:59Z","timestamp":1781513699553,"version":"3.54.1"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"8","license":[{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["CNPq grant # 300830\/2024-6"],"award-info":[{"award-number":["CNPq grant # 300830\/2024-6"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","award":["CNPq grant #303048\/2022-0"],"award-info":[{"award-number":["CNPq grant #303048\/2022-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"name":"National Institute of Science and Technology \u2013 INCT BioNat","award":["CNPq grant # 465637\/2014-0, FAPESP grant # 2014\/50926-0, Brazil"],"award-info":[{"award-number":["CNPq grant # 465637\/2014-0, FAPESP grant # 2014\/50926-0, Brazil"]}]},{"name":"Universidade Federal Do Delta Do Parna\u00edba"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Naunyn-Schmiedeberg's Arch Pharmacol"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Oral squamous cell carcinoma (OSCC), accounts for approximately 90% of oral cancer cases, and due to its aggressive nature and limited treatment options remains a significant clinical challenge. In the pursuit of novel therapeutic agents, bis-chalcones (a subclass of chalcones) have emerged as promising candidates with multipronged anticancer potential. In this study, we synthesized and evaluated a novel bis-chalcone (B2OCH\n                    <jats:sub>3<\/jats:sub>\n                    ), for its cytotoxic, anti-migratory, anti-invasive, and anti-adhesive activities, as well as potential mechanisms of action. The compound was obtained via Claisen\u2013Schmidt condensation and spectroscopically characterized. Cytotoxicity was assessed using MTT, pulse treatment, and trypan blue exclusion assays. Morphological changes were examined with panoptic staining and immunofluorescence. Clonogenic, migration, adhesion, and invasion assays were performed to assess anti-metastatic potential. Molecular docking and gene\/protein expression analyses were conducted by quantitative PCR and Western blot. B2OCH\n                    <jats:sub>3<\/jats:sub>\n                    exhibited potent cytotoxicity against HSC-3, SCC-4, and CAL-27 OSCC cell lines, with HSC-3 being the most sensitive. The compound demonstrated selectivity for cancer cells as compared with non-tumor HS5 and HaCaT cells. Reduced viability was accompanied by mitotic figures and apoptotic bodies. B2OCH\n                    <jats:sub>3<\/jats:sub>\n                    significantly inhibited colony formation, migration, invasion, and adhesion in HSC-3 cells. Morphological analysis revealed modulation of actin filament organization and reduced filopodia formation. Molecular docking indicated MMP-2 and F-actin affinity, and was corroborated by molecular assays confirming protein modulation for both. Our findings identify B2OCH\n                    <jats:sub>3<\/jats:sub>\n                    as a promising therapeutic candidate for OSCC, highlighting its potential to simultaneously target both MMP-2 activity and actin cytoskeleton regulation.\n                  <\/jats:p>","DOI":"10.1007\/s00210-026-05050-0","type":"journal-article","created":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T02:52:18Z","timestamp":1771642338000},"page":"11643-11658","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual inhibition of MMP-2 and actin dynamics by a novel bis-chalcone: an anticancer strategy for oral squamous cell carcinoma"],"prefix":"10.1007","volume":"399","author":[{"given":"Rodrigo El\u00edsio","family":"de S\u00e1","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruna Oliveira","family":"de Almeida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcelo","family":"da Costa Mota","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matheus Pedrosa","family":"de Oliveira","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anali","family":"Del Milagro Bernabe Garnique","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keli","family":"Lima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aline Bernardes","family":"Valeze","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jefferson Almeida","family":"Rocha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caridad Noda","family":"P\u00e9rez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jo\u00e3o Agostinho","family":"Machado Neto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Let\u00edcia Veras","family":"Costa Lotufo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 Delano Barreto","family":"Marinho Filho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7182-7097","authenticated-orcid":false,"given":"Ana J\u00e9rsia","family":"Ara\u00fajo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"key":"5050_CR1","doi-asserted-by":"publisher","unstructured":"Abubakar S, Khairuddean M, Ismail NZ, Salhimi SM, Al-Amin M, Wahyuningsih TD (2024) Synthesis and computational insights of hybrid heterocyclic bis-chalcone compounds and their cytotoxic effects against breast cancer cells. Res Chem 101464. https:\/\/doi.org\/10.1016\/j.rechem.2024101464.","DOI":"10.1016\/j.rechem.2024101464"},{"key":"5050_CR2","doi-asserted-by":"publisher","first-page":"3871","DOI":"10.1016\/j.bmc.2004.05006","volume":"12","author":"BK Adams","year":"2004","unstructured":"Adams BK, Ferstl EM, Davis MC, Herold M, Kurtkaya S, Camalier RF, Hollingshead MG, Kaur G, Sausville EA, Rickles FR, Snyder JP, Liotta DC, Shoji M (2004) Synthesis and biological evaluation of novel curcumin analogs as anti-cancer and anti-angiogenesis agents. Bioorg Med Chem 12:3871\u20133883. https:\/\/doi.org\/10.1016\/j.bmc.2004.05006","journal-title":"Bioorg Med Chem"},{"key":"5050_CR3","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.626577","volume":"11","author":"F Adeshakin","year":"2021","unstructured":"Adeshakin F, Adeshakin AO, Afolabi LO, Yan D, Zhang G, Wan X (2021) Mechanisms for modulating anoikis resistance in cancer and the relevance of metabolic reprogramming. Front Oncol 11:626577. https:\/\/doi.org\/10.3389\/fonc.2021.626577","journal-title":"Front Oncol"},{"key":"5050_CR4","doi-asserted-by":"publisher","first-page":"38","DOI":"10.1016\/j.bcp.2019.06.016","volume":"47","author":"LC Almeida","year":"2019","unstructured":"Almeida LC, Bauermeister A, Rezende-Teixeira P, Santos EAD, Moraes LAB, Machado-Neto JA, Costa-Lotufo LV (2019) Pradimicin-IRD exhibits antineoplastic effects by inducing DNA damage in colon cancer cells. Biochem Pharmacol 47:38\u201347. https:\/\/doi.org\/10.1016\/j.bcp.2019.06.016","journal-title":"Biochem Pharmacol"},{"key":"5050_CR5","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1016\/j.cbi.2024111115","volume":"1","author":"GS Ara\u00fajo","year":"2024","unstructured":"Ara\u00fajo GS, Moura AF, Barros AB, Moraes MO, Pessoa C, Perez CN, Castro MRC, Ribeiro FOS, Silva DAD, Sousa PSA, Rocha JA, Marinho Filho JDB, Araujo AJ (2024) Sulfonamide-chalcone hybrid compound suppresses cellular adhesion and migration: experimental and computational insight. Chem Biol Interact 1:398\u2013111115. https:\/\/doi.org\/10.1016\/j.cbi.2024111115","journal-title":"Chem Biol Interact"},{"key":"5050_CR6","doi-asserted-by":"crossref","unstructured":"Bastrakov M, Starosotnikov A (2022) Recent progress in the synthesis of drugs and bioactive molecules incorporating nitro (het) arene core. Pharmaceuticals (Basel). 15:705. 103390\/ph15060705","DOI":"10.3390\/ph15060705"},{"key":"5050_CR7","doi-asserted-by":"publisher","first-page":"87","DOI":"10.1016\/j.ejmech.2006.08012","volume":"42","author":"D Batovska","year":"2007","unstructured":"Batovska D, Parushev S, Slavova A, Bankova V, Tsvetkova I, Ninova M, Najdenski H (2007) Study on the substituents effects of a series of synthetic chalcones against the yeast Candida albicans. Eur J Med Chem 42:87\u201392. https:\/\/doi.org\/10.1016\/j.ejmech.2006.08012","journal-title":"Eur J Med Chem"},{"key":"5050_CR8","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1093\/nar\/28.1.235","volume":"28","author":"HM Berman","year":"2000","unstructured":"Berman HM, Westbrook J, Feng Z, Gilliland G, Bhat TN, Weissig H, Shindyalov IN, Bourne PE (2000) The protein data bank. Nucleic Acids Res 28:235\u2013242","journal-title":"Nucleic Acids Res"},{"key":"5050_CR9","doi-asserted-by":"publisher","unstructured":"Burmaoglu S, Gobek A, Ozturk Aydin B, Yurtoglu E, Nur Aydin B, Yalcin Ozkat G, Hepokur C, Simsek Ozek N, Aysin F, Altundas R, Algul O (2021) Design, synthesis and biological evaluation of novel bischalcone derivatives as potential anticancer agents. Bioorg Chem 109:104882. https:\/\/doi.org\/10.1016\/j.bioorg.2021.104882","DOI":"10.1016\/j.bioorg.2021.104882"},{"key":"5050_CR10","doi-asserted-by":"publisher","unstructured":"Cabral LGS, Oliveira CS, Oliveira VX Jr, Paulo EPA, Poyet J-L, Maria DA (2025) Evaluation of the antitumor and antiproliferative potential of synthetic peptides derived from IsCT1, associated with cisplatin, in squamous cell carcinoma of the oral cavity. Molecules 30(12):2594. https:\/\/doi.org\/10.3390\/molecules30122594","DOI":"10.3390\/molecules30122594"},{"key":"5050_CR11","doi-asserted-by":"publisher","first-page":"7","DOI":"10.21769\/BioProtoc98","volume":"2","author":"Y Chen","year":"2012","unstructured":"Chen Y (2012) Cell adhesion assay. Bio-Protoc 2:7\u20139. https:\/\/doi.org\/10.21769\/BioProtoc98","journal-title":"Bio-Protoc"},{"issue":"21","key":"5050_CR12","doi-asserted-by":"publisher","first-page":"11306","DOI":"10.3390\/ijms222111306","volume":"22","author":"T Constantinescu","year":"2021","unstructured":"Constantinescu T, Lungu CN (2021) Anticancer activity of natural and synthetic chalcones. Int J Mol Sci 22(21):11306. https:\/\/doi.org\/10.3390\/ijms222111306","journal-title":"Int J Mol Sci"},{"key":"5050_CR13","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.20241354132","volume":"1","author":"RM Crossley","year":"2024","unstructured":"Crossley RM, Johnson S, Tsingos E, Bell Z, Berardi M, Botticelli M, Braat QJS, Metzcar J, Ruscone M, Yin Y, Shuttleworth R (2024) Modeling the extracellular matrix in cell migration and morphogenesis: a guide for the curious biologist. Front Cell Dev Biol 1:1354132. https:\/\/doi.org\/10.3389\/fcell.20241354132","journal-title":"Front Cell Dev Biol"},{"key":"5050_CR14","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcab.2023.102908","volume":"54","author":"RE De S\u00e1","year":"2023","unstructured":"De S\u00e1 RE, Ara\u00fajo GS, Silva JM, Aguiar FP, Silva VL, Silva DAD (2023) Chemical composition, antibacterial and cytotoxic activities of essential oil obtained from aerial parts of Aeschynomene denticulata rudd. Biocatal Agric Biotechnol 54:102908","journal-title":"Biocatal Agric Biotechnol"},{"key":"5050_CR15","doi-asserted-by":"publisher","first-page":"938","DOI":"10.1055\/a-2381-5060","volume":"90","author":"RE De S\u00e1","year":"2024","unstructured":"De S\u00e1 RE, de Ara\u00fajo GS, Machado FDS, Souza JMT, Barros AB, Pinto FDCL, Agostinho JDL, Ayala AP, MarinhoFilho JDB, Pessoa ODL, Ara\u00fajo AJ (2024) Withaphysalin derivatives from Iochroma arborescens induce antiproliferative and antimigratory activities in vitro. Planta Med 90:938\u2013948. https:\/\/doi.org\/10.1055\/a-2381-5060","journal-title":"Planta Med"},{"key":"5050_CR16","doi-asserted-by":"publisher","first-page":"4809","DOI":"10.1080\/14786419.20212000980","volume":"36","author":"PS De Souza","year":"2022","unstructured":"De Souza PS, Bib\u00e1 GCC, Melo EDDN, Muzitano MF (2022) Chalcones against the hallmarks of cancer: a mini-review. Nat Prod Res 36:4809\u20134826. https:\/\/doi.org\/10.1080\/14786419.20212000980","journal-title":"Nat Prod Res"},{"issue":"6","key":"5050_CR17","doi-asserted-by":"publisher","first-page":"2169","DOI":"10.31557\/APJCP.2024.25.6.2169","volume":"25","author":"DAI Eloraby","year":"2024","unstructured":"Eloraby DAI, El-Gayar SF, El-Bolok AH, Ammar SG, ElShafei MM (2024) In vitro assessment of the cytotoxic effect of 5-fluorouracil, thymoquinone and their combination on tongue squamous cell carcinoma cell line. Asian Pac J Cancer Prev 25(6):2169. https:\/\/doi.org\/10.31557\/APJCP.2024.25.6.2169","journal-title":"Asian Pac J Cancer Prev"},{"key":"5050_CR18","doi-asserted-by":"publisher","DOI":"10.3389\/fcell.2022.863721","volume":"10","author":"AD Eren","year":"2022","unstructured":"Eren AD, Lucassen AWA, Tuvshindorj U, Truckenm\u00fcller R, Giselbrecht S, Eren ED, Tas MO, Sudarsanam P, de Boer J (2022) Cells dynamically adapt to surface geometry by remodeling their focal adhesions and actin cytoskeleton. Front Cell Dev Biol 10:863721. https:\/\/doi.org\/10.3389\/fcell.2022.863721","journal-title":"Front Cell Dev Biol"},{"issue":"24","key":"5050_CR19","doi-asserted-by":"publisher","first-page":"6202","DOI":"10.1002\/slct.202100884","volume":"6","author":"EM Fathi","year":"2021","unstructured":"Fathi EM, Sroor FM, Mahrous KF, Mohamed MF, Mahmoud K, Emara M, Elwahy AHM, Abdelhamid IA (2021) Design, synthesis, in silico and in vitro anticancer activity of novel bis-furanyl-chalcone derivatives linked through alkyl spacers. ChemistrySelect 6(24):6202\u20136211. https:\/\/doi.org\/10.1002\/slct.202100884","journal-title":"ChemistrySelect"},{"key":"5050_CR20","doi-asserted-by":"publisher","DOI":"10.7759\/cureus.54394","volume":"16","author":"J Fatima","year":"2024","unstructured":"Fatima J, Fatima E, Mehmood F, Ishtiaq I, Khan MA, Khurshid HMS, Kashif M (2024) Comprehensive analysis of oral squamous cell carcinomas: clinical, epidemiological, and histopathological insights with a focus on prognostic factors and survival time. Cureus 16:e54394. https:\/\/doi.org\/10.7759\/cureus.54394","journal-title":"Cureus"},{"key":"5050_CR21","doi-asserted-by":"publisher","unstructured":"Ferrari IV, Patrizio P (2021) Development and validation molecular docking analysis of human serum albumin (HSA). bioRxiv. https:\/\/doi.org\/10.1101\/2021.07.09.451789","DOI":"10.1101\/2021.07.09.451789"},{"key":"5050_CR22","doi-asserted-by":"publisher","first-page":"3219","DOI":"10.1016\/0040-4020(80)80168-2","volume":"36","author":"J Gasteiger","year":"1980","unstructured":"Gasteiger J, Marsili M (1980) Iterative partial equalization of orbital electronegativity\u2014a rapid access to atomic charges. Tetrahedron 36:3219\u20133228. https:\/\/doi.org\/10.1016\/0040-4020(80)80168-2","journal-title":"Tetrahedron"},{"key":"5050_CR23","doi-asserted-by":"publisher","first-page":"1564","DOI":"10.1016\/j.cell.2023.03003","volume":"186","author":"S Gerstberger","year":"2023","unstructured":"Gerstberger S, Jiang Q, Ganesh K (2023) Metastasis Cell 186:1564\u20131579. https:\/\/doi.org\/10.1016\/j.cell.2023.03003","journal-title":"Metastasis Cell"},{"key":"5050_CR24","doi-asserted-by":"publisher","first-page":"179","DOI":"10.1038\/s41568-019-0112-1","volume":"19","author":"H Hamidi","year":"2019","unstructured":"Hamidi H, Ivaska J (2019) Every step of the way: integrins in cancer progression and metastasis. Nat Rev Cancer 19:179. https:\/\/doi.org\/10.1038\/s41568-019-0112-1","journal-title":"Nat Rev Cancer"},{"key":"5050_CR25","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290CD-21-1059","volume":"12","author":"D Hanahan","year":"2022","unstructured":"Hanahan D (2022) Hallmarks of cancer: new dimensions. Cancer Discov 12:31\u201346. https:\/\/doi.org\/10.1158\/2159-8290CD-21-1059","journal-title":"Cancer Discov"},{"key":"5050_CR26","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1016\/j.oraloncology.2018.11010","volume":"88","author":"S Haque","year":"2019","unstructured":"Haque S, Karivedu V, Riaz MK, Choi D, Roof L, Hassan SZ, Zhu Z, Jandarov R, Takiar V, Tang A, Wise-Draper T (2019) High-risk pathological features at the time of salvage surgery predict poor survival after definitive therapy in patients with head and neck squamous cell carcinoma. Oral Oncol 88:9\u201315. https:\/\/doi.org\/10.1016\/j.oraloncology.2018.11010","journal-title":"Oral Oncol"},{"key":"5050_CR27","doi-asserted-by":"publisher","DOI":"10.1007\/s12672-025-01997-3","volume":"16","author":"L He","year":"2025","unstructured":"He L, Wan M, Yang X, Meng H (2025) Distant metastasis of oral squamous cell carcinoma: immune escape mechanism and new perspectives on treatment. Discov Oncol 16:257. https:\/\/doi.org\/10.1007\/s12672-025-01997-3","journal-title":"Discov Oncol"},{"key":"5050_CR28","doi-asserted-by":"publisher","first-page":"2495","DOI":"10.1074\/jbc.REV119.007759","volume":"295","author":"M Janiszewska","year":"2020","unstructured":"Janiszewska M, Primi MC, Izard T (2020) Cell adhesion in cancer: beyond the migration of single cells. J Biol Chem 295:2495\u20132505. https:\/\/doi.org\/10.1074\/jbc.REV119.007759","journal-title":"J Biol Chem"},{"key":"5050_CR29","doi-asserted-by":"publisher","first-page":"298","DOI":"10.1002\/cpt.1836","volume":"108","author":"R Jansson-L\u00f6fmark","year":"2020","unstructured":"Jansson-L\u00f6fmark R, Hjorth S, Gabrielsson J (2020) Does in vitro potency predict clinically efficacious concentrations? Clin Pharmacol Ther 108:298\u2013305. https:\/\/doi.org\/10.1002\/cpt.1836","journal-title":"Clin Pharmacol Ther"},{"key":"5050_CR30","doi-asserted-by":"publisher","first-page":"2075","DOI":"10.2174\/0929867329666220823112731","volume":"30","author":"IS Kim","year":"2023","unstructured":"Kim IS, Yang WS, Kim CH (2023) Physiological properties, functions, and trends in the matrix metalloproteinase inhibitors in inflammation-mediated human diseases. Curr Med Chem 30:2075\u20132112. https:\/\/doi.org\/10.2174\/0929867329666220823112731","journal-title":"Curr Med Chem"},{"key":"5050_CR31","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41556-024-01409-8","volume":"1","author":"AW Lambert","year":"2024","unstructured":"Lambert AW, Zhang Y, Weinberg RA (2024) Cell-intrinsic and microenvironmental determinants of metastatic colonization. Nat Cell Biol 1:1\u201311. https:\/\/doi.org\/10.1038\/s41556-024-01409-8","journal-title":"Nat Cell Biol"},{"key":"5050_CR32","doi-asserted-by":"publisher","first-page":"509","DOI":"10.1080\/135437762021","volume":"31","author":"E Lenci","year":"2021","unstructured":"Lenci E, Cosottini L, Trabocchi A (2021) Novel matrix metalloproteinase inhibitors: an updated patent review (2014\u20132020). Expert Opin Ther Pat 31:509\u2013523. https:\/\/doi.org\/10.1080\/135437762021","journal-title":"Expert Opin Ther Pat"},{"key":"5050_CR33","doi-asserted-by":"publisher","first-page":"323","DOI":"10.1038\/s41401-020-00525-z","volume":"42","author":"M Li","year":"2021","unstructured":"Li M, Xi N, Wang Y, Liu L (2021) Atomic force microscopy for revealing micro\/nanoscale mechanics in tumor metastasis: from single cells to microenvironmental cues. Acta Pharmacol Sin 42:323\u2013339. https:\/\/doi.org\/10.1038\/s41401-020-00525-z","journal-title":"Acta Pharmacol Sin"},{"key":"5050_CR34","doi-asserted-by":"publisher","first-page":"2623","DOI":"10.1016\/j.bmc.2008.10044","volume":"17","author":"G Liang","year":"2009","unstructured":"Liang G, Shao L, Wang Y, Zhao C, Chu Y, Xiao J, Zhao YX, Yang S (2009) Exploration and synthesis of curcumin analogues with improved structural stability both in vitro and in vivo as cytotoxic agents. Bioorg Med Chem 17:2623\u20132631. https:\/\/doi.org\/10.1016\/j.bmc.2008.10044","journal-title":"Bioorg Med Chem"},{"key":"5050_CR35","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2023.110480","volume":"378","author":"LTF Lima","year":"2023","unstructured":"Lima LTF, Ganzella FAO, Cardoso GC, Pires VDS, Chequin A, Santos GL, Braun-Prado K, Galindo CM, Braz Junior O, Molento MB, Acco A, Adami ER, Costa ET, Franco CRC, Klassen G, Ramos EAS (2023) L-carvone decreases breast cancer cells adhesion, migration, and invasion by suppressing FAK activation. Chem Biol Interact 378:110480. https:\/\/doi.org\/10.1016\/j.cbi.2023.110480","journal-title":"Chem Biol Interact"},{"key":"5050_CR36","doi-asserted-by":"publisher","first-page":"402","DOI":"10.1006\/meth.2001.1262","volume":"25","author":"KJ Livak","year":"2001","unstructured":"Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative pcr and the 2(-delta delta c(t)) method. Methods 25:402\u2013408. https:\/\/doi.org\/10.1006\/meth.2001.1262","journal-title":"Methods"},{"key":"5050_CR37","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.20241406644","volume":"14","author":"A Mancini","year":"2024","unstructured":"Mancini A, Gentile MT, Pentimalli F, Cortellino S, Grieco M, Giordano A (2024) Multiple aspects of matrix stiffness in cancer progression. Front Oncol 14:1406644. https:\/\/doi.org\/10.3389\/fonc.20241406644","journal-title":"Front Oncol"},{"key":"5050_CR38","doi-asserted-by":"publisher","first-page":"3491","DOI":"10.1016\/j.bmc.2006.01.003","volume":"15","author":"A Modzelewska","year":"2006","unstructured":"Modzelewska A, Pettit C, Achanta G, Davidson NE, Huang P, Khan SR (2006) Anticancer activities of novel chalcone and bis-chalcone derivatives. Bioorg Med Chem 15:3491\u20133495. https:\/\/doi.org\/10.1016\/j.bmc.2006.01.003","journal-title":"Bioorg Med Chem"},{"key":"5050_CR39","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/0471250953","volume":"24","author":"GM Morris","year":"2008","unstructured":"Morris GM, Huey R, Olson AJ (2008) Using autodock for ligand-receptor docking. Curr Protoc Bioinform 24:8\u201314. https:\/\/doi.org\/10.1002\/0471250953","journal-title":"Curr Protoc Bioinform"},{"key":"5050_CR40","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1016\/0022-1759(83)90303-4","volume":"65","author":"T Mosmann","year":"1983","unstructured":"Mosmann T (1983) Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods 65:55\u201363. https:\/\/doi.org\/10.1016\/0022-1759(83)90303-4","journal-title":"J Immunol Methods"},{"key":"5050_CR41","doi-asserted-by":"publisher","unstructured":"Nian C, Gan X, Liu Q, Wu Y, Kong M, Zhang P, Jin M, Dong Z, Li W, Wang L, He W (2024) Synthesis and anti-gastric cancer activity by targeting FGFR1 pathway of novel asymmetric bis-chalcone compounds. Curr Med Chem 31(39):6521\u20136541. https:\/\/doi.org\/10.2174\/0109298673298420240530093525","DOI":"10.2174\/0109298673298420240530093525"},{"key":"5050_CR42","doi-asserted-by":"publisher","DOI":"10.1016\/j.heliyon.2024.e31747","volume":"10","author":"D Olender","year":"2024","unstructured":"Olender D, Kujawski J, Sk\u00f3ra B, Baranowska-W\u00f3jcik E, Sowa-Kasprzak K, Pawe\u0142czyk A, Zaprutko L, Szwajgier KA (2024) Bis-chalcones obtained via one-pot synthesis as anti-neurodegenerative agents and their effect on the HT-22 cell line. Heliyon 10:e37147. https:\/\/doi.org\/10.1016\/j.heliyon.2024.e31747","journal-title":"Heliyon"},{"key":"5050_CR43","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-022-01250-x","volume":"8","author":"X Pang","year":"2023","unstructured":"Pang X, He X, Qiu Z, Zhang H, Xie R, Liu Z, Gu Y, Zhao N, Xiang Q, Cui Y (2023) Targeting integrin pathways: mechanisms and advances in therapy. Signal Transduct Target Ther 8:1. https:\/\/doi.org\/10.1038\/s41392-022-01250-x","journal-title":"Signal Transduct Target Ther"},{"key":"5050_CR44","doi-asserted-by":"publisher","first-page":"646","DOI":"10.3390\/jcm8050646","volume":"8","author":"GW Pearson","year":"2019","unstructured":"Pearson GW (2019) Control of invasion by epithelial-to-mesenchymal transition programs during metastasis. J Clin Med 8:646. https:\/\/doi.org\/10.3390\/jcm8050646","journal-title":"J Clin Med"},{"key":"5050_CR45","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023115280","volume":"5","author":"R Pereira","year":"2023","unstructured":"Pereira R, Silva AMS, Ribeiro D, Silva VLM, Fernandes E (2023) Bis-chalcones: a review of synthetic methodologies and anti-inflammatory effects. Eur J Med Chem 5:115280. https:\/\/doi.org\/10.1016\/j.ejmech.2023115280","journal-title":"Eur J Med Chem"},{"key":"5050_CR46","doi-asserted-by":"publisher","unstructured":"Pettersen EF, Goddard TD, Huang CC, Couch GS, Greenblatt DM, Meng EC, Ferrin TE (2004) UCSF Chimera \u2013 a visualization system for exploratory research and analysis. J Comput Chem 25:1605\u20131612. https:\/\/doi.org\/10.1002\/jcc.20084","DOI":"10.1002\/jcc.20084"},{"key":"5050_CR47","doi-asserted-by":"publisher","first-page":"12","DOI":"10.37796\/2211-80391447","volume":"14","author":"P Rajendran","year":"2024","unstructured":"Rajendran P (2024) Unveiling the power of flavonoids: a dynamic exploration of their impact on cancer through matrix metalloproteinases regulation. Biomedicine (Taipei) 14:12\u201328. https:\/\/doi.org\/10.37796\/2211-80391447","journal-title":"Biomedicine (Taipei)"},{"key":"5050_CR48","doi-asserted-by":"publisher","first-page":"787","DOI":"10.1007\/s10822-012-9599-4","volume":"26","author":"MP Repasky","year":"2012","unstructured":"Repasky MP, Shelton HA, Ebe K, Sastry GM, Ebe J, Abel R, Friesner RA (2012) Docking performance of the glide program as evaluated on the Astex and DUD datasets: a complete set of glide SP results and selected results for a new scoring function integrating WaterMap and glide. J Comput Aided Mol Des 26:787\u2013799. https:\/\/doi.org\/10.1007\/s10822-012-9599-4","journal-title":"J Comput Aided Mol Des"},{"key":"5050_CR49","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0198476","volume":"13","author":"JA Rocha","year":"2018","unstructured":"Rocha JA, Rego NC, Carvalho BT, Silva FI, Sousa JA, Ramos RM, Passos ING, Moraes J, Leite JRSA, Lima FC (2018) Computational quantum chemistry, molecular docking, and ADMET predictions of imidazole alkaloids of Pilocarpus microphyllus with schistosomicidal properties. PLoS One 13:e0198476. https:\/\/doi.org\/10.1371\/journal.pone.0198476","journal-title":"PLoS One"},{"issue":"1","key":"5050_CR50","doi-asserted-by":"publisher","DOI":"10.1186\/s40001-024-01657-2","volume":"29","author":"P Sati","year":"2024","unstructured":"Sati P, Sharma E, Dhyani P, Attri DC, Rana R, Kiyekbayeva L, B\u00fcsselberg D, Samuel SM, Sharifi-Rad J (2024) Paclitaxel and its semi-synthetic derivatives: comprehensive insights into chemical structure, mechanisms of action, and anticancer properties. Eur J Med Res 29(1):90. https:\/\/doi.org\/10.1186\/s40001-024-01657-2","journal-title":"Eur J Med Res"},{"key":"5050_CR51","doi-asserted-by":"publisher","first-page":"4711","DOI":"10.1016\/j.bmc.2010.05.015","volume":"18","author":"A Sharma","year":"2010","unstructured":"Sharma A, Chakravarti B, Gupt MP, Siddiqui JA, Konwar R, Tripathi RP (2010) Synthesis and anti breast cancer activity of biphenyl based chalcones. Bioorg Med Chem 18:4711\u20134720. https:\/\/doi.org\/10.1016\/j.bmc.2010.05.015","journal-title":"Bioorg Med Chem"},{"key":"5050_CR52","doi-asserted-by":"publisher","DOI":"10.1038\/s41392-024-01885-2","volume":"9","author":"X Shi","year":"2024","unstructured":"Shi X, Wang X, Yao W, Shi D, Shao X, Lu Z, Chai Y, Song J, Tang W, Wang X (2024) Mechanism insights and therapeutic intervention of tumor metastasis: latest developments and perspectives. Signal Transduct Target Ther 9:192. https:\/\/doi.org\/10.1038\/s41392-024-01885-2","journal-title":"Signal Transduct Target Ther"},{"key":"5050_CR53","doi-asserted-by":"publisher","first-page":"209","DOI":"10.3322\/caac.21660","volume":"71","author":"H Sung","year":"2021","unstructured":"Sung H, Ferlay J, Siegel R, Laversanne J, Soerjomataram I, Jemal A, Bray F (2021) Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 71:209\u2013249. https:\/\/doi.org\/10.3322\/caac.21660","journal-title":"CA Cancer J Clin"},{"key":"5050_CR54","doi-asserted-by":"publisher","first-page":"455","DOI":"10.1002\/jcc.21334","volume":"31","author":"O Trott","year":"2010","unstructured":"Trott O, Olson AJ (2010) Autodock vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading. J Comput Chem 31:455\u2013461. https:\/\/doi.org\/10.1002\/jcc.21334","journal-title":"J Comput Chem"},{"key":"5050_CR55","doi-asserted-by":"publisher","first-page":"3011","DOI":"10.1158\/0008-5472CAN-19-0458","volume":"79","author":"DR Welch","year":"2019","unstructured":"Welch DR, Hurst DR (2019) Defining the hallmarks of metastasis. Can Res 79:3011\u20133027. https:\/\/doi.org\/10.1158\/0008-5472CAN-19-0458","journal-title":"Can Res"},{"key":"5050_CR56","doi-asserted-by":"publisher","DOI":"10.1016\/j.micron.2019102750","volume":"126","author":"H Xiao","year":"2019","unstructured":"Xiao H, Chen Y, Alnaggar M (2019) Silver nanoparticles induce cell death of colon cancer cells through impairing cytoskeleton and membrane nanostructure. Micron 126:102750. https:\/\/doi.org\/10.1016\/j.micron.2019102750","journal-title":"Micron"},{"key":"5050_CR57","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2020173396","volume":"5","author":"J Yang","year":"2020","unstructured":"Yang J, Mu WW, Liu GY (2020) Synthesis and evaluation of the anticancer activity of bis-chalcone analogs in human lung carcinoma (A549) cell line. Eur J Pharmacol 5:173396. https:\/\/doi.org\/10.1016\/j.ejphar.2020173396","journal-title":"Eur J Pharmacol"},{"key":"5050_CR58","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-10400-3","volume":"7","author":"S Zhang","year":"2017","unstructured":"Zhang S, Li T, Zhang L, Wang X, Dong H, Li L, Fu D, Li Y, Zi X, Liu H-M, Zhang Y, Xu H, Jin C-Y (2017) A novel chalcone derivative S17 induces apoptosis through ROS-dependent DR5 up-regulation in gastric cancer cells. Sci Rep 7:10400. https:\/\/doi.org\/10.1038\/s41598-017-10400-3","journal-title":"Sci Rep"},{"key":"5050_CR59","doi-asserted-by":"publisher","first-page":"30296","DOI":"10.1016\/j.bbrc.2020.02030","volume":"291","author":"C Zhao","year":"2020","unstructured":"Zhao C, Hou X, Peng Z, Sun X, Li E, Yang H, Lu Y, Zhu L (2020) Estrogen receptor alpha depletion affects the biomechanical properties and cytoskeleton rearrangements in breast cancer cells. Biochem Biophys Res Commun 291:30296\u201330305. https:\/\/doi.org\/10.1016\/j.bbrc.2020.02030","journal-title":"Biochem Biophys Res Commun"},{"key":"5050_CR60","doi-asserted-by":"publisher","first-page":"7762","DOI":"10.1021\/acs.chemrev.7b00020","volume":"117","author":"C Zhuang","year":"2017","unstructured":"Zhuang C, Zhang W, Sheng C, Zhang W, Xing C, Miao Z (2017) Chalcone: a privileged structure in medicinal chemistry. Chem Rev 117:7762\u20137810. https:\/\/doi.org\/10.1021\/acs.chemrev.7b00020","journal-title":"Chem Rev"}],"container-title":["Naunyn-Schmiedeberg's Archives of Pharmacology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05050-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00210-026-05050-0","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00210-026-05050-0.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,15]],"date-time":"2026-06-15T08:19:24Z","timestamp":1781511564000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00210-026-05050-0"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,2,21]]},"references-count":60,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["5050"],"URL":"https:\/\/doi.org\/10.1007\/s00210-026-05050-0","relation":{},"ISSN":["0028-1298","1432-1912"],"issn-type":[{"value":"0028-1298","type":"print"},{"value":"1432-1912","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,2,21]]},"assertion":[{"value":"28 August 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"22 January 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 February 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent to participate"}},{"value":"Not applicable.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}