{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:35:44Z","timestamp":1786977344895,"version":"build-2736575974"},"reference-count":85,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T00:00:00Z","timestamp":1778630400000},"content-version":"vor","delay-in-days":12,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100005307","name":"Direction G\u00e9n\u00e9rale de la Recherche Scientifique et du D\u00e9veloppement Technologique","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100005307","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry &amp; Biodiversity"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This research presents the design, synthesis, and thorough evaluation of a new series of benzofuran\u20101,4\u2010dihydropyridine hybrids (\n                    <jats:bold>4a\u2013i<\/jats:bold>\n                    ) as potential multi\u2010target anti\u2010inflammatory drugs. These compounds were created through an optimized multistep process and examined using a combination of in silico, in vitro, and in vivo methods. Molecular docking revealed a potential dual\u2010target profile, with the leading compounds showing strong predicted binding to both COX\u20102 and TNF\u2010\u03b1. Notably, compound\n                    <jats:bold>4i<\/jats:bold>\n                    demonstrated the highest affinity for COX\u20102 (MolDock score = \u2212181.002\u00a0kcal\/mol), with good selectivity over COX\u20101 (\u0394 = \u221221.35), and also showed one of the strongest affinities for TNF\u2010\u03b1 (\u2212174.847\u00a0kcal\/mol). Molecular dynamics simulations confirmed the stability of the\n                    <jats:bold>4i<\/jats:bold>\n                    \u2010COX\u20102 complex. This in silico effectiveness was supported by strong in vitro anti\u2010inflammatory activity (eg. 10.09\u00a0\u00b5g\/mL for IC\n                    <jats:sub>50<\/jats:sub>\n                    of\n                    <jats:bold>4b<\/jats:bold>\n                    in hypotonicity\u2010induced hemolysis). Notably, the compounds showed excellent in vivo activity in a carrageenan\u2010induced paw edema model, with\n                    <jats:bold>4i<\/jats:bold>\n                    achieving 91.5% inhibition at 90 min. Histological analysis confirmed that the lead compounds were highly gastrointestinal (GI)\u2010sparing, consistent with their predicted COX\u20102 selectivity. No liver damage was observed, and platelet count remained normal (\n                    <jats:bold>4i<\/jats:bold>\n                    ). Overall, this study identifies compound\n                    <jats:bold>4i<\/jats:bold>\n                    as a potent, orally active, and safe antinflammatory candidate with potential dual mechanisms.\n                  <\/jats:p>","DOI":"10.1002\/cbdv.202503119","type":"journal-article","created":{"date-parts":[[2026,5,13]],"date-time":"2026-05-13T13:04:37Z","timestamp":1778677477000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Design and Synthesis of Benzofuran\u20101,4\u2010dihydropyridine Hybrids as Novel Anti\u2010Inflammatory Agents: Theoretical Exploration of a Potential Dual COX\u20102\/TNF\u2010\u03b1 Mechanism"],"prefix":"10.1002","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6894-0551","authenticated-orcid":false,"given":"Katia Mohand","family":"Saidi","sequence":"first","affiliation":[{"name":"Department of Chemistry Faculty of Exact Sciences and Informatics University of Mohamed Seddik Ben Yahia\u2010Jijel  Ouled Aissa Algeria"},{"name":"Pharmaceutical Team Laboratory of Phytochemistry and Pharmacology University of Mohamed Seddik Ben Yahia\u2010Jijel  Ouled Aissa Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bassam A.","family":"Najri","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Sciences Eskisehir Osmangazi University  Eskisehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7343-0242","authenticated-orcid":false,"given":"Smail","family":"Khelili","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Exact Sciences and Informatics University of Mohamed Seddik Ben Yahia\u2010Jijel  Ouled Aissa Algeria"},{"name":"Pharmaceutical Team Laboratory of Phytochemistry and Pharmacology University of Mohamed Seddik Ben Yahia\u2010Jijel  Ouled Aissa Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kamel","family":"Harrouche","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Exact Sciences and Informatics University of Mohamed Seddik Ben Yahia\u2010Jijel  Ouled Aissa Algeria"},{"name":"Pharmaceutical Team Laboratory of Phytochemistry and Pharmacology University of Mohamed Seddik Ben Yahia\u2010Jijel  Ouled Aissa Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5504-9827","authenticated-orcid":false,"given":"Mohamed Zakaria","family":"Stiti","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Exact Sciences and Informatics University of Mohamed Seddik Ben Yahia\u2010Jijel  Ouled Aissa Algeria"},{"name":"Pharmaceutical Team Laboratory of Phytochemistry and Pharmacology University of Mohamed Seddik Ben Yahia\u2010Jijel  Ouled Aissa Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elyes","family":"Kelai","sequence":"additional","affiliation":[{"name":"Centre De Recherche Scientifique Et Technique En Analyses Physico\u2010Chimiques (CRAPC)  Tipaza Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdelmadjid","family":"Guendouzi","sequence":"additional","affiliation":[{"name":"Chemistry Laboratory: Synthesis Properties and Applications (LCSPA) University of Saida  Saida Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tahir","family":"Habila","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Exact Sciences and Informatics University of Mohamed Seddik Ben Yahia\u2010Jijel  Ouled Aissa Algeria"},{"name":"Department of Physical Sciences Higher Normal School of Boussada  Msila Algeria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif","family":"Kivrak","sequence":"additional","affiliation":[{"name":"Department of Chemistry Faculty of Sciences Eskisehir Osmangazi University  Eskisehir Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,5,13]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557513666131119204126"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2008.02.022"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.sjbs.2018.03.001"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/9783527664450.ch9"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/j.1552\u20104604.1987.tb05576.x"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11696\u2010019\u201000925\u20104"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1023632419813"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.3390\/pharmaceutics11020085"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104379"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11094\u2010015\u20101305\u2010x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2016.05.017"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.2174\/1389557513666131119204126"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.2147\/DDDT.S329547"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.2174\/1573407212666160511124430"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2011.09.023"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2018.10.002"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570193X16666190710122912"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044\u2010013\u20100887\u20105"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1039\/C5RA20658H"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2016.11.007"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.2174\/0122133461272081231102061911"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.4c00424"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570178614666170321125853"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2014.11.039"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/pola.23600"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.4c00424"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.pharep.2016.11.011"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/C7RA01642J"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9RA04917G"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1080\/17460441.2023.2157400"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2010.03.034"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2014.03.087"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2025.142482"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules24081529"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1021\/ar7001279"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026619666190619115735"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1517\/17460441.2010.508069"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/MLR.0b013e3182408812"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.2174\/1568026616666160927160136"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202500374"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.202500895"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpg.2009.11.005"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006\u20102952(00)00576\u20101"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010020\u201077940\u20100"},{"key":"e_1_2_11_46_1","doi-asserted-by":"publisher","DOI":"10.5812\/ijpr\u2010151312"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.105663"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41583\u2010022\u201000592\u20104"},{"key":"e_1_2_11_49_1","unstructured":"https:\/\/www.rcsb.org\/structure\/3KK6."},{"key":"e_1_2_11_50_1","unstructured":"https:\/\/www.rcsb.org\/structure\/6bl3."},{"key":"e_1_2_11_51_1","unstructured":"https:\/\/www.rcsb.org\/structure\/7JRA."},{"key":"e_1_2_11_52_1","volume-title":"ChemDraw Professional. ChemDraw Professional, Version 16 0.0.82","year":"2019"},{"key":"e_1_2_11_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/1758\u20102946\u20103\u201033"},{"key":"e_1_2_11_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/978\u20101\u20104939\u20109752\u20107_10"},{"key":"e_1_2_11_55_1","doi-asserted-by":"crossref","unstructured":"S. S.PawarandS. H.Rohane Review on Discovery Studio: An Important Tool for Molecular Docking (2021) https:\/\/doi.org\/10.5281\/zenodo.5554316.","DOI":"10.5958\/0974-4150.2021.00014.6"},{"key":"e_1_2_11_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s008940100045"},{"key":"e_1_2_11_57_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.saa.2014.12.006"},{"key":"e_1_2_11_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jtice.2016.10.026"},{"key":"e_1_2_11_59_1","unstructured":"O. E. C. D.In OECD Guidelines for the Testing of Chemicals Section 4: Health Effects. Test no. 4 25: Acute Oral Toxicity: Up\u2010and\u2010Down Procedure (2008) https:\/\/doi.org\/10.1787\/9789264071049\u2010en."},{"key":"e_1_2_11_60_1","doi-asserted-by":"publisher","DOI":"10.1787\/9789264078413\u2010en"},{"key":"e_1_2_11_61_1","doi-asserted-by":"publisher","DOI":"10.3181\/00379727\u2010111\u201027849"},{"key":"e_1_2_11_62_1","doi-asserted-by":"publisher","DOI":"10.7763\/IJBBB.2013.V3.218"},{"key":"e_1_2_11_63_1","doi-asserted-by":"publisher","DOI":"10.4172\/2157\u20107099.S4\u2010001"},{"key":"e_1_2_11_64_1","doi-asserted-by":"publisher","DOI":"10.1186\/2008\u20102231\u201020\u201076"},{"key":"e_1_2_11_65_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0367\u2010326X(99)00030\u20101"},{"key":"e_1_2_11_66_1","unstructured":"R.Sarveswaran W. J. A. B.Jayasuriya andT. S.Suresh \u201cIn Vitro Assays to Investigate the Anti\u2010Inflammatory Activity of Herbal Extracts: A Review \u201d (2017)."},{"key":"e_1_2_11_67_1","doi-asserted-by":"publisher","DOI":"10.1080\/10942912.2021.1914083"},{"key":"e_1_2_11_68_1","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/10.6.1003"},{"key":"e_1_2_11_69_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.2042\u20107158.1968.tb09718.x"},{"issue":"4","key":"e_1_2_11_70_1","first-page":"327","article-title":"The in Vitro Anti\u2010Denaturation Effects Induced by Natural Products and Non\u2010Steroidal Compounds in Heat\u2010Treated (immunogenic) Bovine Serum Albumin Are Proposed as a Screening Assay for the Detection of Anti\u2010Inflammatory Compounds, without the use of animals, in the early stages of the drug discovery process","volume":"57","author":"Williams L. A. D.","year":"2008","journal-title":"West Indian Medical Journal"},{"key":"e_1_2_11_71_1","doi-asserted-by":"publisher","DOI":"10.5455\/jice.20160731025522"},{"key":"e_1_2_11_72_1","doi-asserted-by":"publisher","DOI":"10.4324\/9781315614182"},{"issue":"3","key":"e_1_2_11_73_1","first-page":"7","article-title":"Formulation & Evaluation of Voriconazole Ointment for Topical Delivery","volume":"26","author":"Asija R.","year":"2015","journal-title":"Journal of Drug Discovery and Therapeutics"},{"key":"e_1_2_11_74_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745\u20104603.1975.tb01419.x"},{"key":"e_1_2_11_75_1","doi-asserted-by":"publisher","DOI":"10.18637\/jss.v088.i02"},{"key":"e_1_2_11_76_1","doi-asserted-by":"publisher","DOI":"10.21577\/0103\u20105053.20170119"},{"key":"e_1_2_11_77_1","doi-asserted-by":"publisher","DOI":"10.15406\/mojboc.2017.01.00045"},{"key":"e_1_2_11_78_1","doi-asserted-by":"publisher","DOI":"10.1159\/000358638"},{"key":"e_1_2_11_79_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-0716-0524-0_21"},{"key":"e_1_2_11_80_1","doi-asserted-by":"publisher","DOI":"10.1103\/PhysRevLett.126.128101"},{"key":"e_1_2_11_81_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMe020092"},{"key":"e_1_2_11_82_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2003.09.009"},{"key":"e_1_2_11_83_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph11040101"},{"key":"e_1_2_11_84_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10555\u2010017\u20109675\u2010z"},{"key":"e_1_2_11_85_1","doi-asserted-by":"publisher","DOI":"10.1080\/10406638.2022.2105904"},{"key":"e_1_2_11_86_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules28093899"}],"container-title":["Chemistry &amp; Biodiversity"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202503119","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cbdv.202503119","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cbdv.202503119","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T16:00:57Z","timestamp":1785081657000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cbdv.202503119"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5]]},"references-count":85,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2026,5]]}},"alternative-id":["10.1002\/cbdv.202503119"],"URL":"https:\/\/doi.org\/10.1002\/cbdv.202503119","archive":["Portico"],"relation":{},"ISSN":["1612-1872","1612-1880"],"issn-type":[{"value":"1612-1872","type":"print"},{"value":"1612-1880","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5]]},"assertion":[{"value":"2025-09-22","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-04-15","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-05-13","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e03119"}}