{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,27]],"date-time":"2026-03-27T07:50:59Z","timestamp":1774597859665,"version":"3.50.1"},"reference-count":30,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,2,28]],"date-time":"2026-02-28T00:00:00Z","timestamp":1772236800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UID\/50006"],"award-info":[{"award-number":["UID\/50006"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001871","name":"Funda\u00e7\u00e3o para a Ci\u00eancia e a Tecnologia","doi-asserted-by":"publisher","award":["UI\/BD\/151269\/2021"],"award-info":[{"award-number":["UI\/BD\/151269\/2021"]}],"id":[{"id":"10.13039\/501100001871","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Over the past two decades, the search for safe and effective COX\u20102 inhibitors has spurred extensive research on flavonoids. Within this context, synthetic flavonoid dimers have emerged as a promising subclass with potential anti\u2010inflammatory activity. To investigate whether dimerization enhances their potency and selectivity, novel A\u2010fused\n                    <jats:italic>bis<\/jats:italic>\n                    \u2010chalcones and A\u2010fused\n                    <jats:italic>bis<\/jats:italic>\n                    \u2010flavones were synthesized and evaluated for their inhibitory activity against isolated human COX\u20101 and COX\u20102 enzymes, as well as their effects on prostaglandin E\n                    <jats:sub>2<\/jats:sub>\n                    production in whole human blood. Interestingly, the most active compound identified was a monomeric chalcone sharing the same substitution pattern as the top\u2010performing\n                    <jats:italic>bis<\/jats:italic>\n                    \u2010chalcone, suggesting that key structural features drive activity regardless of dimerization. While the dimeric nature of\n                    <jats:italic>bis<\/jats:italic>\n                    \u2010chalcones did not enhance COX\u20102 inhibition or selectivity in this study, these results provide valuable insights into structure\u2013activity relationships. Furthermore, all active compounds against the isolated enzyme showed reduced potency in whole blood, possibly due to plasma protein binding limiting bioavailability. This study highlights the importance of rational design for further development of dimeric flavonoids, in particular strategies aimed at optimizing bioavailability.\n                  <\/jats:p>","DOI":"10.1111\/cbdd.70268","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:10:44Z","timestamp":1772986244000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Evaluation of\n                    <i>Bis<\/i>\n                    \u2010Chalcones and\n                    <i>Bis<\/i>\n                    \u2010Flavones as Selective\n                    <scp>COX<\/scp>\n                    \u20102 Inhibitors"],"prefix":"10.1111","volume":"107","author":[{"given":"Rui","family":"Pereira","sequence":"first","affiliation":[{"name":"LAQV\u2010REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy University of Porto  Porto Portugal"}]},{"given":"Marisa","family":"Freitas","sequence":"additional","affiliation":[{"name":"LAQV\u2010REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy University of Porto  Porto Portugal"}]},{"given":"Alberto N.","family":"Ara\u00fajo","sequence":"additional","affiliation":[{"name":"LAQV\u2010REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy University of Porto  Porto Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0938-5085","authenticated-orcid":false,"given":"Vera L. M.","family":"Silva","sequence":"additional","affiliation":[{"name":"LAQV\u2010REQUIMTE, Department of Chemistry University of Aveiro  Aveiro Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6424-0976","authenticated-orcid":false,"given":"Eduarda","family":"Fernandes","sequence":"additional","affiliation":[{"name":"LAQV\u2010REQUIMTE, Laboratory of Applied Chemistry, Department of Chemical Sciences, Faculty of Pharmacy University of Porto  Porto Portugal"}]}],"member":"311","published-online":{"date-parts":[[2026,2,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1MD00280E"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986708784911579"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.lfs.2020.117631"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmpb.2012.08.017"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-023-37729-2"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.202205735"},{"key":"e_1_2_11_8_1","volume-title":"GaussView, version 6.0.16","author":"Dennington R.","year":"2016"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1021\/ed3006677"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1080\/00397911.2020.1781186"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201300193"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1093-3263(97)00107-1"},{"key":"e_1_2_11_13_1","volume-title":"Gaussian 09, (Revision A.02)","author":"Frisch M. 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