{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T22:30:15Z","timestamp":1793313015692,"version":"4.5.0"},"reference-count":122,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2025,7,1]],"date-time":"2025-07-01T00:00:00Z","timestamp":1751328000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T00:00:00Z","timestamp":1745193600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Foundation for Science and Technology","doi-asserted-by":"publisher","award":["UID\/50006"],"award-info":[{"award-number":["UID\/50006"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["European Journal of Medicinal Chemistry"],"published-print":{"date-parts":[[2025,7]]},"DOI":"10.1016\/j.ejmech.2025.117669","type":"journal-article","created":{"date-parts":[[2025,4,21]],"date-time":"2025-04-21T02:04:23Z","timestamp":1745201063000},"page":"117669","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":10,"special_numbering":"C","title":["Synthetic flavonoid dimers: Synthesis strategies and biological activities"],"prefix":"10.1016","volume":"291","author":[{"given":"Rui","family":"Pereira","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniela","family":"Ribeiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vera L.M.","family":"Silva","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6424-0976","authenticated-orcid":false,"given":"Eduarda","family":"Fernandes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"6","key":"10.1016\/j.ejmech.2025.117669_bib1","doi-asserted-by":"crossref","first-page":"439","DOI":"10.1007\/s13205-013-0117-5","article-title":"Anti-cancer potential of flavonoids: recent trends and future perspectives","volume":"3","author":"Batra","year":"2013","journal-title":"3 Biotech"},{"issue":"2023","key":"10.1016\/j.ejmech.2025.117669_bib2","article-title":"Bis-chalcones: a review of synthetic methodologies and anti-inflammatory effects","volume":"252","author":"Pereira","year":"2023","journal-title":"Eur. J. Med. Chem."},{"issue":"19","key":"10.1016\/j.ejmech.2025.117669_bib3","doi-asserted-by":"crossref","DOI":"10.3390\/molecules26196088","article-title":"Proceedings of chemistry, pharmacology, pharmacokinetics and synthesis of biflavonoids","volume":"26","author":"He","year":"2021","journal-title":"Mol"},{"issue":"2","key":"10.1016\/j.ejmech.2025.117669_bib4","first-page":"59","article-title":"Recent advances in anti-inflammatory synthetic flavonoids as potential drugs","volume":"16","author":"Kim","year":"2010","journal-title":"Nat. Prod. Sci."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117669_bib5","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.clindermatol.2012.08.001","article-title":"Albert Szent-Gy\u00f6rgyi (1893-1986): the scientist who discovered vitamin C","volume":"31","author":"Grzybowski","year":"2013","journal-title":"Clin. Dermatol."},{"issue":"13","key":"10.1016\/j.ejmech.2025.117669_bib6","doi-asserted-by":"crossref","first-page":"4982","DOI":"10.3390\/molecules28134982","article-title":"A review of classification, biosynthesis, biological activities and potential applications of flavonoids","volume":"28","author":"Chen","year":"2023","journal-title":"Mol"},{"issue":"9","key":"10.1016\/j.ejmech.2025.117669_bib7","doi-asserted-by":"crossref","first-page":"1429","DOI":"10.1515\/pac-2013-0919","article-title":"Nomenclature of flavonoids (IUPAC recommendations 2017)","volume":"90","author":"Rauter","year":"2018","journal-title":"Pure Appl. Chem."},{"key":"10.1016\/j.ejmech.2025.117669_bib8","series-title":"Stud. Nat. Prod. Chem.","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/B978-0-444-63929-5.00009-7","article-title":"Chapter 9 - homoisoflavonoids: occurrence, biosynthesis, and biological activity","author":"Castelli","year":"2017"},{"key":"10.1016\/j.ejmech.2025.117669_bib9","series-title":"Flavonoids - from Biosynthesis to Human Health","author":"Abdel-Kader","year":"2017"},{"issue":"10","key":"10.1016\/j.ejmech.2025.117669_bib10","doi-asserted-by":"crossref","first-page":"1381","DOI":"10.3390\/plants11101381","article-title":"Biflavonoids: important contributions to the health benefits of ginkgo (Ginkgo biloba L.)","volume":"11","author":"\u0160amec","year":"2022","journal-title":"Plants"},{"issue":"2","key":"10.1016\/j.ejmech.2025.117669_bib11","doi-asserted-by":"crossref","first-page":"214","DOI":"10.3390\/compounds4020011","article-title":"Antimicrobial activity of dimeric flavonoids","volume":"4","author":"Lopes","year":"2024","journal-title":"Compounds"},{"issue":"2021","key":"10.1016\/j.ejmech.2025.117669_bib12","article-title":"Natural biflavonoids as potential therapeutic agents against microbial diseases","volume":"769","author":"Menezes","year":"2021","journal-title":"Sci. Total Environ."},{"key":"10.1016\/j.ejmech.2025.117669_bib13","article-title":"Exploring the mechanism of flavonoids modification by dimerization strategies and their potential to enhance biological activity","volume":"467","author":"Zou","year":"2025","journal-title":"Food Chem. 2025"},{"issue":"2","key":"10.1016\/j.ejmech.2025.117669_bib14","first-page":"224","article-title":"Manifestation of the dynamics of ultrafast photoprocesses in the transient absorption spectra of diflavonoid solutions","volume":"57","author":"Tikhomirov","year":"2021","journal-title":"Proc. Natl. Acad. Sci. Belarus, Phys. Math. Ser."},{"issue":"11","key":"10.1016\/j.ejmech.2025.117669_bib15","doi-asserted-by":"crossref","first-page":"2495","DOI":"10.1002\/cbdv.200790205","article-title":"Synthesis of biologically relevant biflavanoids \u2013 a review","volume":"4","author":"Rahman","year":"2007","journal-title":"Chem. Biodivers."},{"key":"10.1016\/j.ejmech.2025.117669_bib16","article-title":"Nomenclature of organic chemistry","author":"Favre","year":"2013","journal-title":"The Royal Society of Chemistry"},{"key":"10.1016\/j.ejmech.2025.117669_bib17","article-title":"Estrogenic flavonoids and their molecular mechanisms of action","volume":"114","author":"Kiyama","year":"2023","journal-title":"J. Nutr. Biochem. 2023"},{"issue":"21","key":"10.1016\/j.ejmech.2025.117669_bib18","doi-asserted-by":"crossref","first-page":"4554","DOI":"10.1039\/C7OB00804J","article-title":"Divergent synthesis of biflavonoids yields novel inhibitors of the aggregation of amyloid \u03b2 (1\u201342)","volume":"15","author":"Sum","year":"2017","journal-title":"Org. Biomol. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117669_bib19","first-page":"66","article-title":"Microwave-assisted synthesis of novel bis-flavone dimers as new anticancer agents","volume":"16","author":"Andrew","year":"2019","journal-title":"Lett. Org. Chem."},{"issue":"16","key":"10.1016\/j.ejmech.2025.117669_bib20","doi-asserted-by":"crossref","first-page":"2502","DOI":"10.1080\/00397911.2020.1781186","article-title":"Synthesis and studies of flavone and bis-flavone derivatives","volume":"50","author":"Durgapal","year":"2020","journal-title":"Synth. Commun."},{"issue":"2021","key":"10.1016\/j.ejmech.2025.117669_bib21","article-title":"Biflavonoid as potential 3-chymotrypsin-like protease (3CLpro) inhibitor of SARS-coronavirus","volume":"3","author":"Hartini","year":"2021","journal-title":"Results Chem"},{"issue":"12","key":"10.1016\/j.ejmech.2025.117669_bib22","first-page":"1450","article-title":"Advances in the synthesis of biflavones","volume":"85","author":"Xu","year":"2022","journal-title":"Huaxue Tongbao"},{"issue":"11","key":"10.1016\/j.ejmech.2025.117669_bib23","doi-asserted-by":"crossref","first-page":"1525","DOI":"10.1007\/s12272-009-2104-2","article-title":"New anti-inflammatory synthetic biflavonoid with C-C (6-6\u2033) linkage: differential effects on cyclooxygenase-2 and inducible nitric oxide synthase","volume":"32","author":"Lim","year":"2009","journal-title":"Arch Pharm. Res. (Seoul)"},{"key":"10.1016\/j.ejmech.2025.117669_bib24","doi-asserted-by":"crossref","first-page":"1549","DOI":"10.1039\/C39880001549","article-title":"Total synthesis of 3,3\u2032-biflavone","volume":"23","author":"Jieping","year":"1988","journal-title":"J. Chem. Soc. Chem. Commun."},{"issue":"38","key":"10.1016\/j.ejmech.2025.117669_bib25","doi-asserted-by":"crossref","first-page":"5089","DOI":"10.1016\/j.tet.2018.05.003","article-title":"Synthesis of structurally diverse biflavonoids","volume":"74","author":"Sum","year":"2018","journal-title":"Tetrahedron"},{"issue":"6","key":"10.1016\/j.ejmech.2025.117669_bib26","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1002\/bkcs.11140","article-title":"Synthesis of ochnaflavone analogs and their inhibitory activity on PGE and NO production against LPS-treated RAW 264.7 cells","volume":"38","author":"Pham","year":"2017","journal-title":"Bull. Kor. Chem. Soc."},{"issue":"9","key":"10.1016\/j.ejmech.2025.117669_bib27","doi-asserted-by":"crossref","DOI":"10.3390\/molecules21091230","article-title":"Combinatorial synthesis of structurally diverse triazole-bridged flavonoid dimers and trimers","volume":"21","author":"Sum","year":"2016","journal-title":"Mol"},{"issue":"1","key":"10.1016\/j.ejmech.2025.117669_bib28","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1007\/s10600-014-0870-7","article-title":"Synthesis and characterization of novel unnatural di(8-daidzeinyl)methane","volume":"50","author":"Xiao","year":"2014","journal-title":"Chem. Nat. Compd."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117669_bib29","first-page":"443","article-title":"Bis-chalcones and flavones: synthesis and antimicrobial activity","volume":"70","author":"Husain","year":"2013","journal-title":"Acta Pol. Pharm."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117669_bib30","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.bmcl.2008.11.017","article-title":"Synthesis of biflavones having a 6-O-7'' linkage and effects on cyclooxygenase-2 and inducible nitric oxide synthase","volume":"19","author":"Che","year":"2009","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"30","key":"10.1016\/j.ejmech.2025.117669_bib31","doi-asserted-by":"crossref","first-page":"12210","DOI":"10.1039\/c3ra41451e","article-title":"Bi-nuclear Ru(ii) complexes of bis-chalcone and bis-flavonol: synthesis, characterization, photo cleavage of DNA and topoisomerase I inhibition","volume":"3","author":"Gaur","year":"2013","journal-title":"RSC Adv."},{"issue":"9","key":"10.1016\/j.ejmech.2025.117669_bib32","doi-asserted-by":"crossref","first-page":"2373","DOI":"10.1016\/j.bmcl.2006.01.117","article-title":"Synthesis of phospholipase A2 inhibitory biflavonoids","volume":"16","author":"Chen","year":"2006","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"12","key":"10.1016\/j.ejmech.2025.117669_bib33","doi-asserted-by":"crossref","first-page":"1661","DOI":"10.1211\/jpp.58.12.0014","article-title":"Anti-inflammatory activity of the synthetic C-C biflavonoids","volume":"58","author":"Park","year":"2006","journal-title":"J. Pharm. Pharmacol."},{"issue":"16","key":"10.1016\/j.ejmech.2025.117669_bib34","doi-asserted-by":"crossref","first-page":"2101","DOI":"10.1016\/S0960-894X(01)00382-1","article-title":"Biflavonoids as novel antituberculosis agents","volume":"11","author":"Lin","year":"2001","journal-title":"Bioorg. Med. Chem. Lett."},{"issue":"2","key":"10.1016\/j.ejmech.2025.117669_bib35","first-page":"1489","article-title":"Synthesis of new biheterocycles by a one-pot Sonogashira coupling reaction","volume":"42","author":"Deodhar","year":"2011","journal-title":"Heterocycles (Tokyo)"},{"issue":"44","key":"10.1016\/j.ejmech.2025.117669_bib36","doi-asserted-by":"crossref","first-page":"41816","DOI":"10.1021\/acsomega.3c06503","article-title":"Modular approach for the synthesis and bioactivity profiling of 8,8\u2032-biflavones","volume":"8","author":"Klischan","year":"2023","journal-title":"ACS Omega"},{"issue":"7","key":"10.1016\/j.ejmech.2025.117669_bib37","doi-asserted-by":"crossref","DOI":"10.24820\/ark.5550190.p012.034","article-title":"Synthesis of novel oxa-carbocycle annulated flavones and bis-flavones by ring closing\/cross metathesis","author":"Sydhulu","year":"2023","journal-title":"ARKIVOC (Gainesville, FL, U. S.)"},{"issue":"4","key":"10.1016\/j.ejmech.2025.117669_bib38","doi-asserted-by":"crossref","first-page":"594","DOI":"10.1002\/cmdc.200800413","article-title":"Flavonoid dimers as bivalent modulators for p-glycoprotein-based multidrug resistance: Structure\u2013activity relationships","volume":"4","author":"Chan","year":"2009","journal-title":"ChemMedChem"},{"issue":"5","key":"10.1016\/j.ejmech.2025.117669_bib39","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1021\/jm201121b","article-title":"Amine linked flavonoid fimers as modulators for p-glycoprotein-based multidrug resistance: structure\u2013activity relationship and mechanism of modulation","volume":"55","author":"Chan","year":"2012","journal-title":"J. Med. Chem."},{"issue":"22","key":"10.1016\/j.ejmech.2025.117669_bib40","doi-asserted-by":"crossref","first-page":"9931","DOI":"10.1021\/acs.jmedchem.8b00834","article-title":"Discovery of novel flavonoid dimers to reverse multidrug resistance protein 1 (MRP1, ABCC1) mediated drug resistance in cancers using a high throughput platform with \u201cclick chemistry\u201d","volume":"61","author":"Wong","year":"2018","journal-title":"J. Med. Chem."},{"issue":"18","key":"10.1016\/j.ejmech.2025.117669_bib41","doi-asserted-by":"crossref","first-page":"8578","DOI":"10.1021\/acs.jmedchem.9b00963","article-title":"Triazole bridged flavonoid dimers as potent, nontoxic, and highly selective breast cancer resistance protein (BCRP\/ABCG2) inhibitors","volume":"62","author":"Zhu","year":"2019","journal-title":"J. Med. Chem."},{"issue":"6","key":"10.1016\/j.ejmech.2025.117669_bib42","doi-asserted-by":"crossref","first-page":"1087","DOI":"10.1016\/S0040-4039(96)02475-6","article-title":"The first enantioselective synthesis of optically pure (R)- and (S)-5,5\u2033-dihydroxy-4\u2032,4\u2034,7,7\u2033-tetramethoxy-8,8\u2033-biflavone and the reconfirmation of their absolute configuration","volume":"38","author":"Lin","year":"1997","journal-title":"Tetrahedron Lett."},{"issue":"11","key":"10.1016\/j.ejmech.2025.117669_bib43","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1248\/cpb.10.1032","article-title":"Syntheses of nuclear-substituted flavonoids and allied compounds. IX. Syntheses of tetramethyl ether and dimethyl ether of ginkgetin","volume":"10","author":"Nakazawa","year":"1962","journal-title":"Chem. Pharm. Bull."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117669_bib44","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1248\/cpb.11.283","article-title":"Syntheses of ring-substituted flavonoids and cllied compounds. X. Synthesis of Ginkgetin","volume":"11","author":"Nakazawa","year":"1963","journal-title":"Chem. Pharm. Bull."},{"issue":"4","key":"10.1016\/j.ejmech.2025.117669_bib45","doi-asserted-by":"crossref","first-page":"503","DOI":"10.1016\/0040-4020(76)80071-3","article-title":"New synthesis of biflavones of cupressuflavone series","volume":"32","author":"Ahmad","year":"1976","journal-title":"Tetrahedron"},{"issue":"3","key":"10.1016\/j.ejmech.2025.117669_bib46","first-page":"1249","article-title":"Synthesis of dimer by using copper metal with and without solvent","volume":"13","author":"Bhandange","year":"2001","journal-title":"Asian J. Chem."},{"issue":"8","key":"10.1016\/j.ejmech.2025.117669_bib47","doi-asserted-by":"crossref","first-page":"1075","DOI":"10.1080\/00397919308018584","article-title":"Study on the synthesis of some new biflavonoids. VIII. A new synthesis of C3-linked biflavones, bithioflavones and bithiochromones","volume":"23","author":"Li","year":"1993","journal-title":"Synth. Commun."},{"issue":"10","key":"10.1016\/j.ejmech.2025.117669_bib48","doi-asserted-by":"crossref","first-page":"3060","DOI":"10.1016\/j.bmc.2011.04.010","article-title":"Synthesis and antifungal activities of natural and synthetic biflavonoids","volume":"19","author":"Sagrera","year":"2011","journal-title":"Biorg. Med. Chem."},{"issue":"20","key":"10.1016\/j.ejmech.2025.117669_bib49","doi-asserted-by":"crossref","first-page":"2229","DOI":"10.1016\/S0040-4039(00)79688-2","article-title":"A new strategy for the synthesis of biflavonoids via arylboronic acids","volume":"32","author":"Muller","year":"1991","journal-title":"Tetrahedron Lett."},{"issue":"23","key":"10.1016\/j.ejmech.2025.117669_bib50","doi-asserted-by":"crossref","first-page":"3520","DOI":"10.1080\/00397911.2021.1988643","article-title":"Palladium-catalyzed coupling reactions in flavonoids: a retrospective of recent synthetic approaches","volume":"51","author":"Ramos","year":"2021","journal-title":"Synth. Commun."},{"issue":"13","key":"10.1016\/j.ejmech.2025.117669_bib51","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1055\/s-0033-1352444","article-title":"A novel chemical synthesis of biflavonoid Rhodophyscin","volume":"79","author":"Si","year":"2013","journal-title":"Planta Med."},{"issue":"25","key":"10.1016\/j.ejmech.2025.117669_bib52","doi-asserted-by":"crossref","first-page":"9300","DOI":"10.1021\/jo981186b","article-title":"Total synthesis of robustaflavone, a potential anti-hepatitis B agent","volume":"63","author":"Zembower","year":"1998","journal-title":"J. Org. Chem."},{"issue":"11","key":"10.1016\/j.ejmech.2025.117669_bib53","doi-asserted-by":"crossref","first-page":"467","DOI":"10.4172\/2161-0444.1000302","article-title":"Total synthesis of amentoflavone","volume":"5","author":"Park","year":"2015","journal-title":"Med. Chem."},{"issue":"22","key":"10.1016\/j.ejmech.2025.117669_bib54","doi-asserted-by":"crossref","first-page":"7138","DOI":"10.1016\/j.bmc.2007.07.054","article-title":"Inhibitory effect of synthetic C\u2013C biflavones on various phospholipase A2s activity","volume":"15","author":"Moon","year":"2007","journal-title":"Biorg. Med. Chem."},{"issue":"8","key":"10.1016\/j.ejmech.2025.117669_bib55","doi-asserted-by":"crossref","first-page":"1871","DOI":"10.3987\/COM-10-S(E)36","article-title":"Efficient synthesis of biflavones having a ring-A ring of two flavone units using Suzuki cross-coupling reactions","volume":"81","author":"Nakano","year":"2010","journal-title":"Heterocycles (Tokyo)"},{"issue":"18","key":"10.1016\/j.ejmech.2025.117669_bib56","doi-asserted-by":"crossref","first-page":"5478","DOI":"10.1021\/ja00252a029","article-title":"Palladium-catalyzed coupling of aryl triflates with organostannanes","volume":"109","author":"Echavarren","year":"1987","journal-title":"J. Am. Chem. Soc."},{"issue":"35","key":"10.1016\/j.ejmech.2025.117669_bib57","doi-asserted-by":"crossref","first-page":"8206","DOI":"10.1039\/C9OB01219B","article-title":"Total synthesis of wikstrol A and wikstrol B","volume":"17","author":"Lu","year":"2019","journal-title":"Org. Biomol. Chem."},{"issue":"4","key":"10.1016\/j.ejmech.2025.117669_bib58","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1039\/C6QO00726K","article-title":"Total synthesis of I3,II8-biapigenin and ridiculuflavone A","volume":"4","author":"Lu","year":"2017","journal-title":"Org. Chem. Front."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117669_bib59","doi-asserted-by":"crossref","first-page":"6424","DOI":"10.1038\/s41467-022-34123-w","article-title":"Oxygen mediated oxidative couplings of flavones in alkaline water","volume":"13","author":"Yang","year":"2022","journal-title":"Nat. Commun."},{"issue":"11","key":"10.1016\/j.ejmech.2025.117669_bib60","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.3987\/COM-10-12002","article-title":"Unique phenyl ether type biflavonoids, zizyflavosides A and B with biomimetic synthesis for zizyflavoside A","volume":"81","author":"Mostafa","year":"2010","journal-title":"Heterocycles (Tokyo)"},{"issue":"12","key":"10.1016\/j.ejmech.2025.117669_bib61","doi-asserted-by":"crossref","first-page":"2465","DOI":"10.1351\/pac198254122465","article-title":"Structure and function in the biomimetic synthesis of linear, angular and branched condensed tannins","volume":"54","author":"Roux","year":"1982","journal-title":"Pure Appl. Chem."},{"issue":"13","key":"10.1016\/j.ejmech.2025.117669_bib62","doi-asserted-by":"crossref","DOI":"10.1002\/slct.202300779","article-title":"Oxidative assemblies of flavonoids dimers \u2013 synthesis of dehydrodicatechin A","volume":"8","author":"Pradayrol","year":"2023","journal-title":"ChemistrySelect"},{"issue":"8","key":"10.1016\/j.ejmech.2025.117669_bib63","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1007\/s00894-016-3051-8","article-title":"Dimerization of quercetin, diels-alder vs. radical-coupling approach: a joint thermodynamics, kinetics, and topological study","volume":"22","author":"Fourr\u00e9","year":"2016","journal-title":"J. Mol. Model."},{"issue":"5","key":"10.1016\/j.ejmech.2025.117669_bib64","doi-asserted-by":"crossref","first-page":"1409","DOI":"10.1016\/S0040-4020(01)92970-9","article-title":"Oxidative coupling of apigenin","volume":"26","author":"Molyneux","year":"1970","journal-title":"Tetrahedron"},{"issue":"23","key":"10.1016\/j.ejmech.2025.117669_bib65","doi-asserted-by":"crossref","first-page":"13325","DOI":"10.1039\/C9RA00470J","article-title":"Biocatalytic oxidation of flavone analogues mediated by general biocatalysts: horseradish peroxidase and laccase","volume":"9","author":"Yan","year":"2019","journal-title":"RSC Adv."},{"issue":"47","key":"10.1016\/j.ejmech.2025.117669_bib66","doi-asserted-by":"crossref","first-page":"8615","DOI":"10.1021\/acs.orglett.2c03415","article-title":"Visible-light mediated radical alkylation of flavones: a modular access to nonsymmetrical 3,3\u2033-biflavones","volume":"24","author":"Fregoso-L\u00f3pez","year":"2022","journal-title":"Org. Lett."},{"issue":"2","key":"10.1016\/j.ejmech.2025.117669_bib67","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1021\/ol047718u","article-title":"A simple biomimetic synthesis of dl-chamaejasmine, a anique 3,3\u2018-biflavanone","volume":"7","author":"Li","year":"2005","journal-title":"Org. Lett."},{"issue":"6","key":"10.1016\/j.ejmech.2025.117669_bib68","doi-asserted-by":"crossref","first-page":"1105","DOI":"10.1002\/jccs.200200159","article-title":"Synthesis of 2,2\u2032-biflavanones from flavone via electrolytic reductive coupling","volume":"49","author":"Chen","year":"2002","journal-title":"J. Chin. Chem. Soc."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117669_bib69","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1002\/jccs.200300017","article-title":"Photochemical synthesis of 2,2\u2032-Biflavanones from flavone","volume":"50","author":"Chen","year":"2003","journal-title":"J. Chin. Chem. Soc."},{"issue":"16","key":"10.1016\/j.ejmech.2025.117669_bib70","first-page":"10658","article-title":"Electrosynthesis of a biaurone by controlled dimerization of flavone: mechanistic insight and large-scale application","volume":"85","author":"Hosseini","year":"2020","journal-title":"J. Org. Chem."},{"issue":"11","key":"10.1016\/j.ejmech.2025.117669_bib71","doi-asserted-by":"crossref","first-page":"3219","DOI":"10.5012\/bkcs.2014.35.11.3219","article-title":"Synthesis of ochnaflavone and its inhibitory activity on PGE(2) production","volume":"35","author":"Kim","year":"2014","journal-title":"Bull. Kor. Chem. Soc."},{"issue":"4","key":"10.1016\/j.ejmech.2025.117669_bib72","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1002\/jccs.197000032","article-title":"Synthesis of biflavonyl ethers","volume":"17","author":"Chen","year":"1970","journal-title":"J. Chin. Chem. Soc."},{"issue":"15","key":"10.1016\/j.ejmech.2025.117669_bib73","doi-asserted-by":"crossref","first-page":"2484","DOI":"10.1016\/j.tetlet.2014.03.011","article-title":"Total synthesis of (\u2212)-bis-8,8\u2032-catechinylmethane isolated from cocoa liquor","volume":"55","author":"Pariollaud","year":"2014","journal-title":"Tetrahedron Lett."},{"issue":"23","key":"10.1016\/j.ejmech.2025.117669_bib74","doi-asserted-by":"crossref","first-page":"6742","DOI":"10.1021\/jm060593+","article-title":"Flavonoid dimers as bivalent modulators for P-glycoprotein-based multidrug resistance: synthetic apigenin homodimers linked with defined-length poly(ethylene glycol) spacers increase drug retention and enhance chemosensitivity in resistant cancer cells","volume":"49","author":"Chan","year":"2006","journal-title":"J. Med. Chem."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117669_bib75","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1080\/02678292.2019.1622045","article-title":"Isoflavone-based trimer liquid crystals: synthesis, characterization, thermal and mesomorphic properties evaluations","volume":"47","author":"Mohammad","year":"2020","journal-title":"Liq. Cryst."},{"issue":"48","key":"10.1016\/j.ejmech.2025.117669_bib76","doi-asserted-by":"crossref","first-page":"4633","DOI":"10.1016\/S0040-4039(01)97549-5","article-title":"A new approach to the synthesis of symmetrical biflavones","volume":"12","author":"Ahmad","year":"1971","journal-title":"Tetrahedron Lett."},{"issue":"16","key":"10.1016\/j.ejmech.2025.117669_bib77","article-title":"Synthesis of 5, 5\u2032, 7, 7\u2032\u2010tetramethoxy\u20108, 8\u2032\u2010biflavone","volume":"7","author":"Gandhi","year":"1976","journal-title":"Chem. Informationsdienst"},{"issue":"1","key":"10.1016\/j.ejmech.2025.117669_bib78","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1055\/s-1974-23219","article-title":"The ullmann synthesis of biaryls","volume":"1974","author":"Fanta","year":"1974","journal-title":"Synth. Met."},{"issue":"16","key":"10.1016\/j.ejmech.2025.117669_bib79","doi-asserted-by":"crossref","first-page":"2776","DOI":"10.1055\/s-0030-1258140","article-title":"Total synthesis of 3\u2032,3\u2032\u2032\u2032-binaringenin and related biflavonoids","volume":"2010","author":"Sagrera","year":"2010","journal-title":"Synth. Met."},{"issue":"25","key":"10.1016\/j.ejmech.2025.117669_bib80","doi-asserted-by":"crossref","first-page":"5258","DOI":"10.1021\/acs.orglett.4c01308","article-title":"Application of cyclic diaryliodonium salts in the synthesis of axially chiral natural product analogues","volume":"26","author":"Klischan","year":"2024","journal-title":"Org. Lett."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117669_bib81","first-page":"227","article-title":"Oxidative coupling of phloroacetophenone dimethyl ether, resacetophenone and resacetophenone monomethyl ether using silica-bound FeCl3","volume":"23","author":"Parthasarathy","year":"1984","journal-title":"Indian J. Chem., Sect. B"},{"issue":"5","key":"10.1016\/j.ejmech.2025.117669_bib82","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.1021\/acs.jnatprod.5b00829","article-title":"Design and synthesis of structure-simplified derivatives of gonytolide for the promotion of innate immune responses","volume":"79","author":"Kikuchi","year":"2016","journal-title":"J. Nat. Prod."},{"issue":"21","key":"10.1016\/j.ejmech.2025.117669_bib83","doi-asserted-by":"crossref","first-page":"7222","DOI":"10.1021\/jo970670w","article-title":"Total synthesis and absolute stereochemistry of the natural atropisomer of the biflavone 4\u2018,4\u2018\u2018\u2018,7,7\u2018\u2018-tetra-O-methylcupressuflavone","volume":"62","author":"Li","year":"1997","journal-title":"J. Org. Chem."},{"issue":"18","key":"10.1016\/j.ejmech.2025.117669_bib84","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1002\/anie.199418421","article-title":"Asymmetric synthesis of biaryls by intramolecular oxidative couplings of cyanocuprate intermediates","volume":"33","author":"Lipshutz","year":"1994","journal-title":"Angew Chem. Int. Ed. Engl."},{"issue":"10","key":"10.1016\/j.ejmech.2025.117669_bib85","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.6023\/cjoc201503029","article-title":"First total synthesis of (\u00b1)-2,3,2\",3\"-tetrahydroochnaflavone","volume":"35","author":"Yingpeng","year":"2015","journal-title":"Chin. J. Org. Chem."},{"key":"10.1016\/j.ejmech.2025.117669_bib86","doi-asserted-by":"crossref","first-page":"1346","DOI":"10.3762\/bjoc.9.152","article-title":"Total synthesis of ochnaflavone","volume":"9","author":"Ndoile","year":"2013","journal-title":"Beilstein J. Org. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117669_bib87","first-page":"53","article-title":"A comprehensive review of the oxidative cyclisation of 2\u2019-hydroxychalcones to aurones and flavones","volume":"3","author":"Masesane","year":"2015","journal-title":"Int. J. Chem. Stud."},{"issue":"15","key":"10.1016\/j.ejmech.2025.117669_bib88","doi-asserted-by":"crossref","first-page":"169","DOI":"10.3998\/ark.5550190.0007.f20","article-title":"Synthesis of I-3, 11-3-bis-(methylthio)biflavones from the corresponding bichalcones: a new application of the I2-Me2SO-H2SO4 reagent system","volume":"2006","author":"Iqbal","year":"2006","journal-title":"ARKIVOC (Gainesville, FL, U. S.)"},{"key":"10.1016\/j.ejmech.2025.117669_bib89","series-title":"Comprehensive Organic Name Reactions and Reagents","first-page":"168","article-title":"Baker-Venkataraman rearrangement","author":"Wang","year":"2010"},{"issue":"13","key":"10.1016\/j.ejmech.2025.117669_bib90","doi-asserted-by":"crossref","first-page":"3781","DOI":"10.1016\/j.bmc.2015.03.084","article-title":"Synthesis and discovery of (I-3,II-3)-biacacetin as a novel non-zinc binding inhibitor of MMP-2 and MMP-9","volume":"23","author":"Nanjan","year":"2015","journal-title":"Biorg. Med. Chem."},{"issue":"2","key":"10.1016\/j.ejmech.2025.117669_bib91","doi-asserted-by":"crossref","first-page":"573","DOI":"10.1016\/0031-9422(95)00340-D","article-title":"The first biaurone, a triflavone and biflavonoids from two Aulacomnium species","volume":"40","author":"Hahn","year":"1995","journal-title":"Phytochemistry"},{"issue":"23","key":"10.1016\/j.ejmech.2025.117669_bib92","doi-asserted-by":"crossref","first-page":"9647","DOI":"10.1039\/D0NJ00758G","article-title":"Bisaurones \u2013 enzymatic production and biological evaluation","volume":"44","author":"Novakovic","year":"2020","journal-title":"New J. Chem."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117669_bib93","doi-asserted-by":"crossref","first-page":"1531","DOI":"10.1111\/1750-3841.16947","article-title":"Efficient enzymatic synthesis of theaflavin and its production mechanism","volume":"89","author":"Jian","year":"2024","journal-title":"J. Food Sci."},{"issue":"8","key":"10.1016\/j.ejmech.2025.117669_bib94","doi-asserted-by":"crossref","first-page":"736","DOI":"10.1002\/jccs.202400024","article-title":"Recent progress in the preparation of theaflavins: \u201csynthesis, extraction and purification\u201d","volume":"71","author":"Wang","year":"2024","journal-title":"J. Chin. Chem. Soc."},{"key":"10.1016\/j.ejmech.2025.117669_bib95","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.bse.2017.09.004","article-title":"Biflavonoids from Fumana procumbens (dunal) gren. & godr","volume":"74","author":"G\u00fcrb\u00fcz","year":"2017","journal-title":"Biochem. Syst. Ecol. 2017"},{"key":"10.1016\/j.ejmech.2025.117669_bib96","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1039\/b505071p","article-title":"Furanoflavonoids: an overview","volume":"22","author":"Maurya","year":"2005","journal-title":"Nat. Prod. Rep."},{"issue":"14","key":"10.1016\/j.ejmech.2025.117669_bib97","doi-asserted-by":"crossref","first-page":"5420","DOI":"10.3390\/molecules28145420","article-title":"Spiro-flavonoids in nature: a critical review of structural diversity and bioactivity","volume":"28","author":"Pecio","year":"2023","journal-title":"Mol"},{"issue":"31","key":"10.1016\/j.ejmech.2025.117669_bib98","doi-asserted-by":"crossref","first-page":"8104","DOI":"10.1021\/acs.jafc.0c03380","article-title":"Synthesis of A-type proanthocyanidins and their analogues: a comprehensive review","volume":"68","author":"Alejo-Armijo","year":"2020","journal-title":"J. Agric. Food Chem."},{"issue":"12","key":"10.1016\/j.ejmech.2025.117669_bib99","doi-asserted-by":"crossref","first-page":"3007","DOI":"10.3390\/molecules13123007","article-title":"Chemical synthesis of proanthocyanidins in vitro and their reactions in aging wines","volume":"13","author":"He","year":"2008","journal-title":"Mol"},{"issue":"11","key":"10.1016\/j.ejmech.2025.117669_bib100","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1055\/s-0030-1270908","article-title":"Towards the synthesis of proanthocyanidins: half a century of innovation","volume":"77","author":"Ferreira","year":"2011","journal-title":"Planta Med."},{"issue":"3","key":"10.1016\/j.ejmech.2025.117669_bib101","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1007\/s12272-001-1151-3","article-title":"Biochemical pharmacology of biflavonoids: implications for anti-inflammatory action","volume":"31","author":"Kim","year":"2008","journal-title":"Arch Pharm. Res. (Seoul)"},{"issue":"2","key":"10.1016\/j.ejmech.2025.117669_bib102","doi-asserted-by":"crossref","first-page":"117","DOI":"10.4062\/biomolther.2022.004","article-title":"The long search for pharmacologically useful anti-inflammatory flavonoids and their action mechanisms: past, present, and future","volume":"30","author":"Kim","year":"2022","journal-title":"Biomol. Ther."},{"key":"10.1016\/j.ejmech.2025.117669_bib103","article-title":"A new biflavonoid glycoside from the aerial parts of rare and endangered plant Alsophila spinulosa","volume":"112","author":"Jin","year":"2024","journal-title":"Biochem. Syst. Ecol. 2024"},{"issue":"4","key":"10.1016\/j.ejmech.2025.117669_bib104","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1007\/s13659-021-00298-w","article-title":"Hinokiflavone and related C\u2013O\u2013C-type biflavonoids as anti-cancer compounds: properties and mechanism of action","volume":"11","author":"Goossens","year":"2021","journal-title":"Nat. prod. bioprospect"},{"key":"10.1016\/j.ejmech.2025.117669_bib105","article-title":"Insights into amentoflavone: a natural multifunctional biflavonoid","volume":"12","author":"Xiong","year":"2021","journal-title":"Front. Pharmacol. 2021"},{"issue":"5","key":"10.1016\/j.ejmech.2025.117669_bib106","first-page":"21","article-title":"A biflavonoid compound: its pharmacological activity and therapeutic efficacy","volume":"18","author":"Damilare","year":"2022","journal-title":"Curr. Bioact. Compd."},{"issue":"1","key":"10.1016\/j.ejmech.2025.117669_bib107","doi-asserted-by":"crossref","first-page":"230S","DOI":"10.1093\/ajcn\/81.1.230S","article-title":"Bioavailability and bioefficacy of polyphenols in humans. I. Review of 97 bioavailability studies","volume":"81","author":"Manach","year":"2005","journal-title":"Am. J. Clin. Nutr."},{"issue":"21","key":"10.1016\/j.ejmech.2025.117669_bib108","doi-asserted-by":"crossref","first-page":"5230","DOI":"10.1021\/ja000575w","article-title":"Design of bifunctional antibiotics that target bacterial rRNA and inhibit resistance-causing enzymes","volume":"122","author":"Sucheck","year":"2000","journal-title":"J. Am. Chem. Soc."},{"issue":"17","key":"10.1016\/j.ejmech.2025.117669_bib109","doi-asserted-by":"crossref","first-page":"5311","DOI":"10.1021\/jm900194w","article-title":"Modulation of multidrug resistance protein 1 (MRP1\/ABCC1)-mediated multidrug resistance by bivalent apigenin homodimers and their derivatives","volume":"52","author":"Wong","year":"2009","journal-title":"J. Med. Chem."},{"key":"10.1016\/j.ejmech.2025.117669_bib110","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.bcp.2016.10.013","article-title":"Flavonoid dimers are highly potent killers of multidrug resistant cancer cells overexpressing MRP1","volume":"124","author":"Dury","year":"2017","journal-title":"Biochem. Pharmacol. 2017"},{"issue":"1","key":"10.1016\/j.ejmech.2025.117669_bib111","doi-asserted-by":"crossref","first-page":"211","DOI":"10.1007\/s10555-012-9402-8","article-title":"Reversal of ATP-binding cassette drug transporter activity to modulate chemoresistance: why has it failed to provide clinical benefit?","volume":"32","author":"Yu","year":"2013","journal-title":"Cancer Metastasis Rev."},{"issue":"21","key":"10.1016\/j.ejmech.2025.117669_bib112","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232113261","article-title":"Characterization of a potent, selective, and safe inhibitor, Ac15(Az8)2, in reversing multidrug resistance mediated by breast cancer resistance protein (BCRP\/ABCG2)","volume":"23","author":"Chong","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"8","key":"10.1016\/j.ejmech.2025.117669_bib113","doi-asserted-by":"crossref","first-page":"5556","DOI":"10.1007\/s12035-019-1469-6","article-title":"Procyanidins and alzheimer's disease","volume":"56","author":"Zhao","year":"2019","journal-title":"Mol. Neurobiol."},{"key":"10.1016\/j.ejmech.2025.117669_bib114","series-title":"Natural Compounds as Therapeutic Agents for Amyloidogenic Diseases","first-page":"55","article-title":"Biflavonoids as potential small molecule therapeutics for alzheimer's disease","author":"Thapa","year":"2015"},{"issue":"4","key":"10.1016\/j.ejmech.2025.117669_bib115","doi-asserted-by":"crossref","first-page":"1149","DOI":"10.3390\/molecules27041149","article-title":"Antibacterial effects of flavonoids and their structure-activity relationship study: a comparative interpretation","volume":"27","author":"Shamsudin","year":"2022","journal-title":"Mol"},{"issue":"6","key":"10.1016\/j.ejmech.2025.117669_bib116","doi-asserted-by":"crossref","first-page":"1179","DOI":"10.1093\/jac\/dkp130","article-title":"Quinacrine and a novel apigenin dimer can synergistically increase the pentamidine susceptibility of the protozoan parasite Leishmania","volume":"63","author":"Wong","year":"2009","journal-title":"J. Antimicrob. Chemother."},{"issue":"6","key":"10.1016\/j.ejmech.2025.117669_bib117","doi-asserted-by":"crossref","first-page":"3379","DOI":"10.1128\/AAC.02425-13","article-title":"In vitro and in vivo efficacy of novel flavonoid dimers against cutaneous Leishmaniasis","volume":"58","author":"Wong Iris","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"issue":"20","key":"10.1016\/j.ejmech.2025.117669_bib118","doi-asserted-by":"crossref","first-page":"8891","DOI":"10.1021\/jm301172v","article-title":"Flavonoid dimers as novel, potent antileishmanial agents","volume":"55","author":"Wong","year":"2012","journal-title":"J. Med. Chem."},{"issue":"5","key":"10.1016\/j.ejmech.2025.117669_bib119","doi-asserted-by":"crossref","DOI":"10.1128\/AAC.02165-20","article-title":"Amine-linked flavonoids as agents against cutaneous Leishmaniasis","volume":"65","author":"Chan","year":"2021","journal-title":"Antimicrob. Agents Chemother."},{"issue":"15","key":"10.1016\/j.ejmech.2025.117669_bib120","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.2174\/138527211796367354","article-title":"Recent progress in the synthesis of flavonoids: from monomers to supra-complex molecules","volume":"15","author":"Kin-ichi","year":"2011","journal-title":"Curr. Org. Chem."},{"issue":"23","key":"10.1016\/j.ejmech.2025.117669_bib121","doi-asserted-by":"crossref","DOI":"10.3390\/ijms232315299","article-title":"Discovery of a flavonoid FM04 as a potent inhibitor to reverse p-glycoprotein-mediated drug resistance in xenografts and improve oral bioavailability of paclitaxel","volume":"23","author":"Kan","year":"2022","journal-title":"Int. J. Mol. Sci."},{"issue":"9","key":"10.1016\/j.ejmech.2025.117669_bib122","doi-asserted-by":"crossref","first-page":"6160","DOI":"10.1021\/acs.jmedchem.2c02005","article-title":"Identification of binding sites in the nucleotide-binding domain of p-glycoprotein for a potent and nontoxic modulator, the amine-containing monomeric flavonoid FM04","volume":"66","author":"Liu","year":"2023","journal-title":"J. Med. Chem."}],"container-title":["European Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425004349?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0223523425004349?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2026,5,6]],"date-time":"2026-05-06T04:39:45Z","timestamp":1778042385000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0223523425004349"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7]]},"references-count":122,"alternative-id":["S0223523425004349"],"URL":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117669","relation":{},"ISSN":["0223-5234"],"issn-type":[{"value":"0223-5234","type":"print"}],"subject":[],"published":{"date-parts":[[2025,7]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Synthetic flavonoid dimers: Synthesis strategies and biological activities","name":"articletitle","label":"Article Title"},{"value":"European Journal of Medicinal Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.ejmech.2025.117669","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2025 The Authors. Published by Elsevier Masson SAS.","name":"copyright","label":"Copyright"}],"article-number":"117669"}}