{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,9,12]],"date-time":"2024-09-12T05:50:23Z","timestamp":1726120223366},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2021,12,12]],"date-time":"2021-12-12T00:00:00Z","timestamp":1639267200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001807","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado de S\u00e3o Paulo","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001807","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002322","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":[[2022,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Considering the emergence of antifungal resistance on <jats:italic>Sporothrix brasiliensis<\/jats:italic>, we aimed to assess new benzylidene\u2010carbonyl compounds against feline\u2010borne <jats:italic>S<\/jats:italic>. <jats:italic>brasiliensis<\/jats:italic> isolates. The compounds were designed as bioisosteres from previously reported benzylidene\u2010ketones generating the <jats:italic>p<\/jats:italic>\u2010coumaric (<jats:bold>1<\/jats:bold>), cinnamic (<jats:bold>2<\/jats:bold>), <jats:italic>p<\/jats:italic>\u2010methoxycinnamic (<jats:bold>3<\/jats:bold>) and caffeic acid (<jats:bold>4<\/jats:bold>) analogues. The corresponding compounds were tested against feline isolates of <jats:italic>S<\/jats:italic>. <jats:italic>brasiliensis<\/jats:italic> with sensitivity (<jats:italic>n\u00a0<\/jats:italic>=\u00a04) and resistance (<jats:italic>n\u00a0<\/jats:italic>=\u00a05) to itraconazole (ITZ), following the M38\u2010A2 protocol (CLSI, Reference method for broth dilution antifungal susceptibility testing of filamentous fungi M38\u2013A2 Guideline, 2008). Eleven analogues showed activity against all fungal strains with minimum inhibitory concentrations (MIC) \u22641\u00a0mg\/ml (<jats:bold>1a\u2010d<\/jats:bold>, <jats:bold>2e<\/jats:bold>, <jats:bold>3b<\/jats:bold>, <jats:bold>3e<\/jats:bold>, <jats:bold>4<\/jats:bold>, <jats:bold>4a<\/jats:bold> and <jats:bold>5e<\/jats:bold>) and fungicidal concentrations (MFC) \u22641\u00a0mg\/ml (<jats:bold>1b<\/jats:bold>, <jats:bold>1d<\/jats:bold>, <jats:bold>3e<\/jats:bold> and <jats:bold>4a<\/jats:bold>), whereas <jats:bold>3<\/jats:bold> was the less active with both MIC and MFC values above 1\u00a0mg\/ml. Compound <jats:bold>3e<\/jats:bold> (4\u2010methoxy\u2010N\u2010butylcinnamamide) was the most potent (MIC<jats:sub>range<\/jats:sub> 0.08\u20130.16\u00a0mg\/ml; MFC<jats:sub>range<\/jats:sub> 0.32\u20130.64\u00a0mg\/ml) from the set, suggesting a different role of the substituents in ester and amide derivatives. The designed compounds proved to be important prototypes with improved drug\u2010likeness to achieve compounds with higher activity against ITZ\u2010resistant <jats:italic>S<\/jats:italic>. <jats:italic>brasiliensis<\/jats:italic>.<\/jats:p>","DOI":"10.1111\/cbdd.13994","type":"journal-article","created":{"date-parts":[[2021,12,7]],"date-time":"2021-12-07T05:25:15Z","timestamp":1638854715000},"page":"391-397","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Bioisosteric modification on benzylidene\u2010carbonyl compounds improved the drug\u2010likeness and maintained the antifungal activity against <i>Sporothrix brasiliensis<\/i>"],"prefix":"10.1111","volume":"99","author":[{"given":"Stefanie Bressan","family":"Waller","sequence":"first","affiliation":[{"name":"Department of Preventive Veterinary Faculty of Veterinary Federal University of Pelotas  Pelotas RS Brazil"},{"name":"Department of Veterinary Clinics Faculty of Veterinary Federal University of Pelotas  Pelotas RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marlete Brum","family":"Cleff","sequence":"additional","affiliation":[{"name":"Department of Veterinary Clinics Faculty of Veterinary Federal University of Pelotas  Pelotas RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rcia Kutscher","family":"Ripoll","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Faculty of Veterinary Federal University of Pelotas  Pelotas RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rio Carlos Ara\u00fajo","family":"Meireles","sequence":"additional","affiliation":[{"name":"Department of Preventive Veterinary Faculty of Veterinary Federal University of Pelotas  Pelotas RS Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M\u00e1rcio","family":"Ferrarini","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Institute of Environmental, Chemical and Pharmaceutical Sciences Federal University of S\u00e3o Paulo  Diadema SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina Themoteo","family":"Varela","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Institute of Environmental, Chemical and Pharmaceutical Sciences Federal University of S\u00e3o Paulo  Diadema SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jo\u00e3o Paulo S.","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences Institute of Environmental, Chemical and Pharmaceutical Sciences Federal University of S\u00e3o Paulo  Diadema SP Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2021,12,12]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201900544"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1439-0507.1989.tb02294.x"},{"key":"e_1_2_5_4_1","volume-title":"Reference method for broth dilution antifungal susceptibility testing of filamentous fungi M38\u2013A2 Guideline","author":"CLSI \u2013 Clinical and Laboratory Standard Institute","year":"2008"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01057-17"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.3201\/eid2603.190803"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2672.1999.00646.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1080\/14786419.2017.1317776"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42770-020-00290-5"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejps.2020.105473"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1590\/abd1806-4841.2017279"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1155\/2020\/6345429"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1005638"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/jof6040247"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.diagmicrobio.2016.08.002"},{"key":"e_1_2_5_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2020.104108"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12223-020-00814-4"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42770-020-00307-z"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s42770-020-00280-7"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0176189"}],"container-title":["Chemical Biology &amp; Drug Design"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13994","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cbdd.13994","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cbdd.13994","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,27]],"date-time":"2023-08-27T16:32:54Z","timestamp":1693153974000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cbdd.13994"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,12]]},"references-count":19,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2022,3]]}},"alternative-id":["10.1111\/cbdd.13994"],"URL":"https:\/\/doi.org\/10.1111\/cbdd.13994","archive":["Portico"],"relation":{},"ISSN":["1747-0277","1747-0285"],"issn-type":[{"value":"1747-0277","type":"print"},{"value":"1747-0285","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,12]]},"assertion":[{"value":"2021-03-15","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-12-12","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}