{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T20:59:34Z","timestamp":1789937974297,"version":"4.0.1"},"reference-count":27,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2013,11,4]],"date-time":"2013-11-04T00:00:00Z","timestamp":1383523200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2014,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We have conducted systematic structural modification, deconstruction, and reconstruction of the berberine core with the aim of lowering its cytotoxicity, investigating its pharmacophore, and ultimately, seeking novel synergistic agents to restore the effectiveness of fluconazole against fluconazole\u2010resistant <jats:italic>Candida albicans.<\/jats:italic> A structure\u2013activity relationship study of 95 analogues led us to identify the novel scaffold of <jats:italic>N<\/jats:italic>\u2010(2\u2010(benzo[<jats:italic>d<\/jats:italic>][1,3]dioxol\u20105\u2010yl)ethyl)\u20102\u2010(substituted phenyl)acetamides <jats:bold>7\u2009a<\/jats:bold>\u2013<jats:bold>l<\/jats:bold>, which exhibited remarkable levels of in vitro synergistic antifungal activity. Compound <jats:bold>7\u2009d<\/jats:bold> (<jats:italic>N<\/jats:italic>\u2010(2\u2010(benzo[<jats:italic>d<\/jats:italic>][1,3]dioxol\u20105\u2010yl)ethyl)\u20102\u2010(2\u2010fluorophenyl)acetamide) significantly decreased the MIC<jats:sub>80<\/jats:sub> values of fluconazole from 128.0\u2005\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup> to 0.5\u2005\u03bcg\u2009mL<jats:sup>\u22121<\/jats:sup> against fluconazole\u2010resistant <jats:italic>C.\u2005albicans<\/jats:italic> and exhibited much lower levels of cytotoxicity than berberine toward human umbilical vein endothelial cells.<\/jats:p>","DOI":"10.1002\/cmdc.201300332","type":"journal-article","created":{"date-parts":[[2013,11,4]],"date-time":"2013-11-04T10:33:12Z","timestamp":1383561192000},"page":"207-216","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":24,"title":["Structural Optimization of Berberine as a Synergist to Restore Antifungal Activity of Fluconazole against Drug\u2010Resistant <i>Candida albicans<\/i>"],"prefix":"10.1002","volume":"9","author":[{"given":"Hong","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maomao","family":"An","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shaolong","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongbing","family":"Cao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhihui","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhu","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhan","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Dai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tingjunhong","family":"Ni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simin","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changqing","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chengxu","family":"Zang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shujuan","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyu","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunfu","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazhi","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hua","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanying","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2013,11,4]]},"reference":[{"key":"e_1_2_6_1_2","doi-asserted-by":"publisher","DOI":"10.1086\/378745"},{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.9.4.499"},{"key":"e_1_2_6_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki473"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1038\/452541a"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1159746"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/587101"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2011.06.105"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01728-09"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01397-07"},{"key":"e_1_2_6_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1472-765X.2010.02900.x"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-695X.2009.00620.x"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.3.1096-1099.2006"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1248\/bpb.28.541"},{"key":"e_1_2_6_14_2","doi-asserted-by":"publisher","DOI":"10.1208\/s12249-010-9520-y"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.3109\/00498254.2010.529180"},{"key":"e_1_2_6_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpba.2007.03.022"},{"key":"e_1_2_6_17_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.fct.2010.01.033"},{"key":"e_1_2_6_18_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0378-8741(00)00177-X"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm801157z"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0040-4020(01)00826-2"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2006.03.088"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tet.2009.02.024"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo982019e"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo035149i"},{"key":"e_1_2_6_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2012.10.042"},{"key":"e_1_2_6_26_2","unstructured":"P.\u2005A. Wayne Approved standard M27\u2010A3: Clinical and Laboratory Standards Institute (CLSI): USA 2008."},{"key":"e_1_2_6_27_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg301"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201300332","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201300332","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T08:32:46Z","timestamp":1760257966000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201300332"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,11,4]]},"references-count":27,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2014,1]]}},"alternative-id":["10.1002\/cmdc.201300332"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201300332","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,11,4]]},"assertion":[{"value":"2013-08-09","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-11-04","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}