{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T06:04:35Z","timestamp":1769839475574,"version":"3.49.0"},"reference-count":38,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T00:00:00Z","timestamp":1594166400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Vice-Chancellor for Research, Shiraz University of Medical Sciences, Iran","award":["95-01-103-12178"],"award-info":[{"award-number":["95-01-103-12178"]}]},{"name":"Vice-Chancellor for Research, Shiraz University of Medical Sciences, Iran","award":["98-01-36-20126"],"award-info":[{"award-number":["98-01-36-20126"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Archiv der Pharmazie"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>In this study, benzyl\u20101,2,3\u2010triazole\u2010linked 5\u2010benzylidene (thio)barbiturate derivatives <jats:bold>7a<\/jats:bold>\u2013<jats:bold>d<\/jats:bold> and <jats:bold>8a<\/jats:bold>\u2013<jats:bold>h<\/jats:bold> were designed as potential tyrosinase inhibitors and free\u2010radical scavengers. The twelve derivatives were synthesized <jats:italic>via<\/jats:italic> the [3+2] cycloaddition reaction of the corresponding benzyl azide as a dipole and the corresponding alkyne as a dipolarophile in the presence of copper(I) species, generated in situ from copper(II)\/ascorbate. The thiobarbiturate derivative <jats:bold>8h<\/jats:bold> and the barbiturate derivative <jats:bold>8b<\/jats:bold> bearing 4\u2010fluoro and 4\u2010bromo groups on the benzyl\u2013triazole moiety were found to be the most potent tyrosinase inhibitors with IC<jats:sub>50<\/jats:sub> values of 24.6\u2009\u00b1\u20090.9 and 26.8\u2009\u00b1\u20090.8\u2009\u03bcM, respectively. Almost all the compounds showed a good radical scavenging activity with EC<jats:sub>50<\/jats:sub> values in the range of 29.9\u2013324.9\u2009\u03bcM. Derivatives <jats:bold>7a<\/jats:bold>, <jats:bold>8f<\/jats:bold>, and <jats:bold>8h<\/jats:bold> were the most potent free\u2010radical scavengers with EC<jats:sub>50<\/jats:sub> values of 29.9\u2009\u00b1\u20090.8, 36.8\u2009\u00b1\u20090.9, and 39.2\u2009\u00b1\u20091.1\u2009\u03bcM, respectively. The kinetic analysis revealed that compound <jats:bold>8h<\/jats:bold> was a mixed\u2010type tyrosinase inhibitor. The molecular docking analysis indicated that <jats:bold>8b<\/jats:bold> and <jats:bold>8h<\/jats:bold> were well accommodated in the active site of the tyrosinase enzyme and possessed the most negative binding energy values of \u22128.55 and \u22128.81\u2009kcal\/mol, respectively. Moreover, it was found that the two residues, Asn81 and Glu322, played a significant role in forming stable enzyme\u2013inhibitor complexes.<\/jats:p>","DOI":"10.1002\/ardp.202000058","type":"journal-article","created":{"date-parts":[[2020,7,8]],"date-time":"2020-07-08T08:55:40Z","timestamp":1594198540000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["1,2,3\u2010Triazole\u2010linked 5\u2010benzylidene (thio)barbiturates as novel tyrosinase inhibitors and free\u2010radical scavengers"],"prefix":"10.1002","volume":"353","author":[{"given":"Sara","family":"Ranjbar","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Parisa\u2010sadat","family":"Shahvaran","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Najmeh","family":"Edraki","sequence":"additional","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahsima","family":"Khoshneviszadeh","sequence":"additional","affiliation":[{"name":"Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahdieh","family":"Darroudi","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Chemistry University of Mazandaran  Babolsar Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yaghoub","family":"Sarrafi","sequence":"additional","affiliation":[{"name":"Department of Organic Chemistry, Faculty of Chemistry University of Mazandaran  Babolsar Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mahshid","family":"Hamzehloueian","sequence":"additional","affiliation":[{"name":"Department of Chemistry, Jouybar Branch Islamic Azad University  Jouybar Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1458-2964","authenticated-orcid":false,"given":"Mehdi","family":"Khoshneviszadeh","sequence":"additional","affiliation":[{"name":"Department of Medicinal Chemistry, School of Pharmacy Shiraz University of Medical Sciences  Shiraz Iran"},{"name":"Medicinal and Natural Products Chemistry Research Center Shiraz University of Medical Sciences  Shiraz Iran"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,7,8]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/jf020826f"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)96973-5"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.7831\/ras.7.41"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2016.1256882"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms11031082"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1541-4337.2012.00191.x"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1473-2165.2008.00387.x"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jdermsci.2009.06.003"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms10062440"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jfluchem.2012.06.032"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules20033582"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-2952(82)90260-X"},{"key":"e_1_2_7_14_1","first-page":"329","volume":"1","author":"L\u00f3pez\u2010Mu\u00f1oz F.","year":"2005","journal-title":"Neuropsychiatr. Dis. Treat"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1213\/00000539-192901000-00133"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00044-007-9072-1"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2015.10.019"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/slct.201800832"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.12.053"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmgm.2011.07.001"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.05.055"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12010-013-0486-6"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2009.06.018"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2014.04.060"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2009.05.023"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.2174\/092986712803414213"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2019.102967"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2016.02.041"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2013.10.032"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2017.05.001"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2017.10.071"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.01.044"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2018.08.033"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbdv.201800120"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.2174\/157018008784619889"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.2298\/JSC170618038D"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570180815666180219155027"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2019.04.016"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijbiomac.2019.05.201"}],"container-title":["Archiv der Pharmazie"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fardp.202000058","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202000058","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/ardp.202000058","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ardp.202000058","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,6]],"date-time":"2023-09-06T00:55:51Z","timestamp":1693961751000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ardp.202000058"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,7,8]]},"references-count":38,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1002\/ardp.202000058"],"URL":"https:\/\/doi.org\/10.1002\/ardp.202000058","archive":["Portico"],"relation":{},"ISSN":["0365-6233","1521-4184"],"issn-type":[{"value":"0365-6233","type":"print"},{"value":"1521-4184","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,7,8]]},"assertion":[{"value":"2020-02-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-15","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-07-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"2000058"}}