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To tackle the challenges, novel antifungal agents with anti\u2010resistant potency are highly desirable. Thus, derivatives of curcumin were synthesized to restore the effectiveness of fluconazole (FLC) against FLC\u2010resistant <jats:italic>Candida<\/jats:italic> spp. and structure\u2010activity relationships were then discussed. Some novel derivatives showed promising features as novel antifungal lead compounds. Of them, compound <jats:bold>4<\/jats:bold> showed good alone or synergistic antifungal activity against FLC\u2010resistant <jats:italic>Candida<\/jats:italic> spp. Moreover, compound <jats:bold>4<\/jats:bold> was proven as a potent inhibitor of <jats:italic>Candida albicans<\/jats:italic> biofilm formation and yeast\u2010to\u2010hypha morphological transition whether used alone or in combination with FLC, which was further confirmed by the inhibitory effect on cellular surface hydrophobicity of <jats:italic>C.\u00a0albicans<\/jats:italic>. Compound <jats:bold>4<\/jats:bold> also inhibits intracellular ATP production of <jats:italic>C.\u00a0albicans<\/jats:italic> and disrupts membrane permeability of <jats:italic>C.\u00a0albicans<\/jats:italic> when used in combination with FLC. The results highlighted the potential of curcumin derivatives to overcome fluconazole\u2010related and biofilm\u2010related drug resistance.<\/jats:p>","DOI":"10.1111\/cbdd.13827","type":"journal-article","created":{"date-parts":[[2021,1,28]],"date-time":"2021-01-28T07:54:12Z","timestamp":1611820452000},"page":"1079-1088","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Synergistic antifungal effects of curcumin derivatives as fungal biofilm inhibitors with fluconazole"],"prefix":"10.1111","volume":"97","author":[{"given":"Huai\u2010Huai","family":"Dong","sequence":"first","affiliation":[{"name":"School of Pharmacy Second Military Medical University Shanghai China"},{"name":"Department of Pharmacy The Air Force Hospital of Northern Theater PLA Shenyang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Hua","family":"Wang","sequence":"additional","affiliation":[{"name":"Yue\u2010yang Hospital of Integrative Medicine Shanghai University of Traditional Chinese Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue\u2010Mi","family":"Peng","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"He\u2010Yang","family":"Zhou","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fei","family":"Zhao","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan\u2010Ying","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology Shanghai Tenth People's Hospital Tongji University School of Medicine Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0043-7379","authenticated-orcid":false,"given":"Da\u2010Zhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong\u2010Sheng","family":"Jin","sequence":"additional","affiliation":[{"name":"School of Pharmacy Second Military Medical University Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,2,5]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1021\/mp700113r"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01223-07"},{"key":"e_1_2_7_4_1","first-page":"81","article-title":"Polyphenolic antioxidants and neuronal regeneration","volume":"7","author":"Ataie A.","year":"2016","journal-title":"Basic and Clinical Neuroscience"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2015.03.031"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1196\/annals.1329.055"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejphar.2015.12.038"},{"key":"e_1_2_7_8_1","volume-title":"Reference method for broth dilution antifungal susceptibility testing of yeasts, approved standard M27\u2013A3","author":"CLSI","year":"2008"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00651-13"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01242-08"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/jhet.2707"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2012.12.098"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1080\/07391102.2016.1185380"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1973"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2008.10.044"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201300332"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0103442"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1139\/W10-117"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1021\/np060263s"},{"key":"e_1_2_7_20_1","first-page":"346","article-title":"Synthesis, characterization and antimicrobial evaluation of isoxazole derivatives","volume":"7","author":"Raju G. 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