{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T08:53:40Z","timestamp":1768985620965,"version":"3.49.0"},"reference-count":29,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T00:00:00Z","timestamp":1676073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100002428","name":"Austrian Science Fund","doi-asserted-by":"publisher","award":["T942"],"award-info":[{"award-number":["T942"]}],"id":[{"id":"10.13039\/501100002428","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2023,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Selective cyclooxygenase (COX)\u20101 inhibitors can be employed as potential cardioprotective drugs. Moreover, COX\u20101 plays a key role in inflammatory processes and its activity is associated with some types of cancer. In this work, we designed and synthesized a set of compounds that structurally mimic the selective COX\u20101 inhibitors, SC\u2010560 and mofezolac, the central cores of which were replaced either with triazole or benzene rings. The advantage of this approach is a relatively simple synthesis in comparison with the syntheses of parent compounds. The newly synthesized compounds exhibited remarkable activity and selectivity toward COX\u20101 in the enzymatic in vitro assay. The most potent compound, <jats:bold>10a<\/jats:bold> (IC<jats:sub>50<\/jats:sub>\u2009=\u20093\u2009nM for COX\u20101 and 850\u2009nM for COX\u20102), was as active as SC\u2010560 (IC<jats:sub>50<\/jats:sub>\u00a0=\u00a02.4\u00a0nM\u00a0for\u00a0COX\u20101 and\u00a0470\u00a0nM\u00a0for\u00a0COX\u20102)\u00a0toward COX\u20101 and it was even more selective. The in vitro COX\u20101 enzymatic activity was further confirmed in the cell\u2010based whole\u2010blood antiplatelet assay, where three out of four selected compounds (<jats:bold>10a,c,d<\/jats:bold>, and <jats:bold>3b<\/jats:bold>) exerted outstanding IC<jats:sub>50<\/jats:sub> values in the nanomolar range (9\u2013252\u2009nM). Moreover, docking simulations were performed to reveal key interactions within the COX\u20101 binding pocket. Furthermore, the toxicity of the selected compounds was tested using the normal human kidney HK\u20102 cell line.<\/jats:p>","DOI":"10.1002\/ardp.202200549","type":"journal-article","created":{"date-parts":[[2023,2,11]],"date-time":"2023-02-11T09:49:48Z","timestamp":1676108988000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["SC\u2010560 and mofezolac isosteres as new potent COX\u20101 selective inhibitors with antiplatelet effect"],"prefix":"10.1002","volume":"356","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4960-2048","authenticated-orcid":false,"given":"Miroslav","family":"Sisa","sequence":"first","affiliation":[{"name":"Laboratory of Plant Biotechnologies Institute of Experimental Botany of the Czech Academy of Sciences  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9649-1884","authenticated-orcid":false,"given":"Luk\u00e1\u0161","family":"Kone\u010dn\u00fd","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy in Hradec Kralov\u00e9 Charles University  Hradec Kralov\u00e9 Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7662-9882","authenticated-orcid":false,"given":"Veronika","family":"Temml","sequence":"additional","affiliation":[{"name":"Department of Pharmacy\/Pharmacognosy and Center of Molecular Biosciences (CMBI) University of Innsbruck  Innsbruck Austria"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-7981","authenticated-orcid":false,"given":"Alejandro","family":"Carazo","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy in Hradec Kralov\u00e9 Charles University  Hradec Kralov\u00e9 Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6076-6900","authenticated-orcid":false,"given":"P\u0159emysl","family":"Mlad\u011bnka","sequence":"additional","affiliation":[{"name":"Faculty of Pharmacy in Hradec Kralov\u00e9 Charles University  Hradec Kralov\u00e9 Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0364-2247","authenticated-orcid":false,"given":"P\u0159emysl","family":"Landa","sequence":"additional","affiliation":[{"name":"Laboratory of Plant Biotechnologies Institute of Experimental Botany of the Czech Academy of Sciences  Prague Czech Republic"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,2,11]]},"reference":[{"key":"e_1_2_7_2_1","unstructured":"World Health Organization Cardiovascular diseases https:\/\/www.who.int\/health-topics\/cardiovascular-diseases#tab=tab_1 2022(accessed: June 2022)."},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-051019-102940"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199405053301808"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jacc.2006.10.003"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrd1929"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986710793205408"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0179809"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.6361-11.2013"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1097\/00000542-200410000-00025"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2017.00251"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM200108093450607"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph11040101"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.1c00004"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2020.112919"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.b20-00991"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.12.029"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2016.11.037"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.12.023"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm301905a"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0031-12911042"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10593-010-0452-y"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201300858"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2004-5-9-241"},{"key":"e_1_2_7_25_1","first-page":"205","volume":"6","author":"Teng X. 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