{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,10]],"date-time":"2026-09-10T22:31:53Z","timestamp":1789079513011,"version":"build-2803163510"},"reference-count":52,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T00:00:00Z","timestamp":1717545600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1I1A3A04037486, 2022R1C1C2006146, 2021R1A2C1008368"],"award-info":[{"award-number":["2021R1I1A3A04037486, 2022R1C1C2006146, 2021R1A2C1008368"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p><jats:italic>Candida<\/jats:italic> species comprise a ubiquitous pathogenic fungal genus responsible for causing candidiasis. They are one of the primary causatives of several mucosal and systemic infections in humans and can survive in various environments. In this study, we investigated the antifungal, anti-biofilm, and anti-hyphal effects of six <jats:italic>N<\/jats:italic>-substituted phthalimides against three <jats:italic>Candida<\/jats:italic> species. Of the derivatives, <jats:italic>N<\/jats:italic>-butylphthalimide (NBP) was the most potent, with a minimum inhibitory concentration (MIC) of 100 \u00b5g\/ml and which dose-dependently inhibited biofilm at sub-inhibitory concentrations (10\u201350 \u00b5g\/ml) in both the fluconazole-resistant and fluconazole-sensitive <jats:italic>Candida albicans<\/jats:italic> and <jats:italic>Candida parapsilosis<\/jats:italic>. NBP also effectively inhibited biofilm formation in other pathogens including uropathogenic <jats:italic>Escherichia coli<\/jats:italic>, <jats:italic>Staphylococcus epidermidis<\/jats:italic>, <jats:italic>Staphylococcus aureus<\/jats:italic>, and <jats:italic>Vibrio parahaemolyticus<\/jats:italic>, along with the polymicrobial biofilms of <jats:italic>S. epidermidis<\/jats:italic> and <jats:italic>C. albicans<\/jats:italic>. NBP markedly inhibited the hyphal formation and cell aggregation of <jats:italic>C. albicans<\/jats:italic> and altered its colony morphology in a dose-dependent manner. Gene expression analysis showed that NBP significantly downregulated the expression of important hyphal- and biofilm-associated genes, i.e., <jats:italic>ECE1<\/jats:italic>, <jats:italic>HWP1<\/jats:italic>, and <jats:italic>UME6<\/jats:italic>, upon treatment. NBP also exhibited mild toxicity at concentrations ranging from 2 to 20 \u00b5g\/ml in a nematode model. Therefore, this study suggests that NBP has anti-biofilm and antifungal potential against various <jats:italic>Candida<\/jats:italic> strains.<\/jats:p>","DOI":"10.3389\/fcimb.2024.1414618","type":"journal-article","created":{"date-parts":[[2024,6,5]],"date-time":"2024-06-05T04:41:28Z","timestamp":1717562488000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Antifungal, anti-biofilm, and anti-hyphal properties of N-substituted phthalimide derivatives against Candida species"],"prefix":"10.3389","volume":"14","author":[{"given":"Shamshe","family":"Shaik","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin-Hyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yong-Guy","family":"Kim","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jintae","family":"Lee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,6,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"57","DOI":"10.1590\/S0036-46652015000700011","article-title":"Susceptibility test for fungi: clinical and laboratorial correlations in medical mycology","volume":"57","author":"Alastruey-Izquierdo","year":"2015","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1186\/s40543-019-0177-1","article-title":"Investigation of DNA binding and molecular docking propensity of phthalimide derivatives: in vitro antibacterial and antioxidant assay","volume":"10","author":"Arif","year":"2019","journal-title":"J. Anal. Sci. Technol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"337","DOI":"10.1007\/s00726-023-03232-1","article-title":"Novel N-\u03b1-amino acid spacer-conjugated phthalimide\u2013triazine derivatives: synthesis, antimicrobial and molecular docking studies","volume":"55","author":"Asadi","year":"2023","journal-title":"Amino Acids"},{"key":"B4","doi-asserted-by":"publisher","first-page":"1354","DOI":"10.1091\/mbc.e07-11-1110","article-title":"UME6, a novel filament-specific regulator of Candida albicans hyphal extension and virulence","volume":"19","author":"Banerjee","year":"2008","journal-title":"Mol. Biol. Cell"},{"key":"B5","doi-asserted-by":"publisher","first-page":"649","DOI":"10.1016\/j.ejmech.2016.07.066","article-title":"X-ray crystal structures of Enterococcus faecalis thymidylate synthase with folate binding site inhibitors","volume":"123","author":"Catalano","year":"2016","journal-title":"Eur. J. Med. Chem."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1002\/jps.2600721127","article-title":"Hypolipidemic activity of phthalimide derivatives IV: further chemical modification and investigation of the hypolipidemic activity of N-substituted imides","volume":"72","author":"Chapman","year":"1983","journal-title":"J. Pharm. Sci."},{"key":"B7","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1007\/s00044-021-02823-5","article-title":"Synthesis, antiproliferative, and antimicrobial properties of novel phthalimide derivatives","volume":"31","author":"Chi","year":"2022","journal-title":"Med. Chem. Res."},{"key":"B8","first-page":"133","article-title":"Phthalimide derivatives of pyrimidine and thiazole heterocyclics","volume":"31","author":"Cingolani","year":"1976","journal-title":"Farmaco Sci."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3390\/jof4010010","article-title":"Candida albicans hyphae: from growth initiation to invasion","volume":"4","author":"Desai","year":"2018","journal-title":"J. Fungus"},{"key":"B10","doi-asserted-by":"publisher","first-page":"1859","DOI":"10.3390\/polym13111859","article-title":"Synthesis and in-vitro antimicrobial evaluation of photoactive multi-block chalcone conjugate phthalimide and 1,8-naphthalimide novolacs","volume":"13","author":"Durairaju","year":"2021","journal-title":"Polymers"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.202300599","article-title":"Phthalimide-tethered isatins as novel poly(ADP-ribose) polymerase inhibitors: Design, synthesis, biological evaluations, and molecular modeling investigations","volume":"357","author":"El Hassab","year":"2024","journal-title":"Arch. Pharm. Chem. Life Sci."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1346","DOI":"10.1002\/ddr.22094","article-title":"Phthalimide as a versatile pharmacophore scaffold: unlocking its diverse biological activities","volume":"84","author":"Fernandes","year":"2023","journal-title":"Drug Dev. Res."},{"key":"B13","doi-asserted-by":"publisher","first-page":"1806","DOI":"10.1080\/10406638.2020.1809468","article-title":"An efficient synthesis of phthalimides and their biological activities","volume":"42","author":"Jelali","year":"2022","journal-title":"Polycycl. Aromat. Comp."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1007\/s12257-024-00097-3","article-title":"Inhibitory effects of bromoindoles on Escherichia coli O157:H7 biofilms","author":"Jeon","year":"2024","journal-title":"Biotechnol. Bioprocess Eng"},{"key":"B15","doi-asserted-by":"publisher","first-page":"939","DOI":"10.1097\/CCM.0000000000004371","article-title":"Key takeaways from the U.S. CDC\u2019s 2019 antibiotic resistance threats report for frontline providers","volume":"48","author":"Kadri","year":"2020","journal-title":"Crit. Care Med."},{"key":"B16","doi-asserted-by":"publisher","first-page":"494","DOI":"10.2174\/157018006778194862","article-title":"Synthesis and biological evaluation of coumarin linked fluoroquinolones, phthalimides and naphthalimides as potential DNA gyrase inhibitors","volume":"3","author":"Kamal","year":"2006","journal-title":"Lett. Drug Des. Discovery"},{"key":"B17","doi-asserted-by":"publisher","first-page":"e02536","DOI":"10.1128\/spectrum.02536-22","article-title":"Hydroquinones including tetrachlorohydroquinone inhibit Candida albicans biofilm formation by repressing hyphae-related genes","volume":"10","author":"Kim","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"B18","doi-asserted-by":"publisher","first-page":"590","DOI":"10.1111\/1751-7915.13864","article-title":"Inhibition of polymicrobial biofilm formation by saw palmetto oil, lauric acid and myristic acid","volume":"15","author":"Kim","year":"2022","journal-title":"Microb. Biotechnol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"83","DOI":"10.1089\/aivt.2022.0004","article-title":"Characterizing local acute irritation properties of captan and folpet with new approach methods","volume":"8","author":"Kluxen","year":"2022","journal-title":"Appl. Vitro Toxicol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1111\/1751-7915.13710","article-title":"Antibiofilm and antifungal activities of medium-chain fatty acids against Candida albicans via mimicking of the quorum-sensing molecule farnesol","volume":"14","author":"Lee","year":"2021","journal-title":"Microb. Biotechnol."},{"key":"B21","doi-asserted-by":"publisher","first-page":"1353","DOI":"10.1111\/1751-7915.13710","article-title":"Antibiofilm and antifungal activities of medium-chain fatty acids against Candida albicans via mimicking of the quorum-sensing molecule farnesol","volume":"14","author":"Lee","year":"2021","journal-title":"Microb. Biotechnol."},{"key":"B22","doi-asserted-by":"publisher","first-page":"620","DOI":"10.1038\/s41586-024-07142-4","article-title":"The hyphal-specific toxin candidalysin promotes fungal gut commensalism","volume":"627","author":"Liang","year":"2024","journal-title":"Nature"},{"key":"B23","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1080\/21505594.2021.2019950","article-title":"Pathogenesis and virulence of Candida albicans","volume":"13","author":"Lopes","year":"2022","journal-title":"Virulence"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.cdc.2019.100198","article-title":"Design, synthesis, antibiofilm, quorum sensing inhibition, anticancer and docking studies of novel 2-(4-acridine-9-ylamino)isoindoline-1,3-dione","volume":"20","author":"Mane","year":"2019","journal-title":"CDC"},{"key":"B25","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1007\/s00294-013-0400-3","article-title":"Recent insights into Candida albicans biofilm resistance mechanisms","volume":"59","author":"Math\u00e9","year":"2013","journal-title":"Curr. Genet."},{"key":"B26","doi-asserted-by":"publisher","first-page":"e202204851","DOI":"10.1002\/slct.202204851","article-title":"Phthalimides represent a promising scaffold for multi-targeted anticancer agents","volume":"8","author":"Matore","year":"2023","journal-title":"ChemistrySelect"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.meegid.2022.105256","article-title":"Genome plasticity in Candida albicans: A cutting-edge strategy for evolution, adaptation, and survival","volume":"99","author":"Mba","year":"2022","journal-title":"Infect. Genet. Evol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1016\/j.polymdegradstab.2017.04.019","article-title":"Evaluation of the stability of rigid poly(vinyl chloride)\/biologically active phthalimido phenyl urea composites using thermogravimetric analysis","volume":"140","author":"Mohamed","year":"2017","journal-title":"Polym. Degrad. Stab."},{"key":"B29","doi-asserted-by":"publisher","first-page":"829","DOI":"10.1002\/bio.3259","article-title":"New phthalimide-appended schiff bases: Studies of DNA binding, molecular docking and antioxidant activities","volume":"32","author":"Nayab","year":"2017","journal-title":"Luminescence"},{"key":"B30","doi-asserted-by":"publisher","first-page":"3","DOI":"10.3329\/bjp.v10i3.23637","article-title":"Synthesis, spectroscopic studies of novel N-substituted phthalimides and evaluation of their antibacterial, antioxidant, DNA binding and molecular docking studies","volume":"10","author":"Nayab","year":"2015","journal-title":"Bangladesh J. Pharmacol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"159","DOI":"10.7324\/JAPS.2016.60330","article-title":"Recent advances and future prospects of phthalimide derivatives","volume":"3","author":"Neelottama Kushwaha","year":"2016","journal-title":"J. Appl. Pharm. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1016\/j.micres.2015.06.009","article-title":"Usnic acid inhibits biofilm formation and virulent morphological traits of Candida albicans","volume":"179","author":"Nithyanand","year":"2015","journal-title":"Microbiol. Res."},{"key":"B33","doi-asserted-by":"publisher","first-page":"1604","DOI":"10.1128\/EC.00194-06","article-title":"Function of candida albicans adhesin Hwp1 in biofilm formation","volume":"5","author":"Nobile","year":"2006","journal-title":"Eukaryotic Cell"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1259","DOI":"10.1080\/14756366.2019.1637861","article-title":"Novel phthalimide based analogues: design, synthesis, biological evaluation, and molecular docking studies","volume":"34","author":"Othman","year":"2019","journal-title":"J. Enzyme Inhib. Med. Chem."},{"key":"B35","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1016\/j.micpath.2016.04.012","article-title":"Synthesis of N-substituted phthalimides and their antifungal activity against Alternaria solani and Botrytis cinerea","volume":"95","author":"Pan","year":"2016","journal-title":"Microb. Pathog."},{"key":"B36","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/nrdp.2018.26","article-title":"Invasive candidiasis","volume":"4","author":"Pappas","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1186\/2191-2858-3-8","article-title":"Design and synthesis of tetrahydrophthalimide derivatives as inhibitors of HIV-1 reverse transcriptase","volume":"3","author":"Penta","year":"2013","journal-title":"Org. Med. Chem. Lett."},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.carbpol.2021.118882","article-title":"Amphiphilic quaternized chitosan: Synthesis, characterization, and anti-cariogenic biofilm property","volume":"277","author":"Phuangkaew","year":"2022","journal-title":"Carbohydr. Polym."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1336773","article-title":"Isobavachalcone exhibits antifungal and antibiofilm effects against C. albicans by disrupting cell wall\/membrane integrity and inducing apoptosis and autophagy","volume":"14","author":"Qian","year":"2024","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"1266","DOI":"10.1111\/jam.2018.125.issue-5","article-title":"Inhibitory effects of deoxynivalenol on pathogenesis of Candida albicans","volume":"125","author":"Rajasekharan","year":"2018","journal-title":"J. Appl. Microbiol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1002\/yea.3855","article-title":"Living together: The role of Candida albicans in the formation of polymicrobial biofilms in the oral cavity","volume":"40","author":"Rapala-Kozik","year":"2023","journal-title":"Yeast"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics11070877","article-title":"Invasive candidiasis: update and current challenges in the management of this mycosis in south america","volume":"11","author":"Riera","year":"2022","journal-title":"Antibiotics"},{"key":"B43","doi-asserted-by":"publisher","first-page":"10100","DOI":"10.1021\/acs.jpcb.9b09278","article-title":"Amino-acid-based ionic liquids for the improvement in stability and activity of cytochrome c: A combined experimental and molecular dynamics study","volume":"123","author":"Sahoo","year":"2019","journal-title":"J. Phys. Chem. B."},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2024.1340910","article-title":"Antibacterial and antibiofilm activity of halogenated phenylboronic acids against Vibrio parahaemolyticus and Vibrio harveyi","volume":"14","author":"Sathiyamoorthi","year":"2024","journal-title":"Front. Cell Infect. Microbiol."},{"key":"B45","doi-asserted-by":"publisher","first-page":"313","DOI":"10.2174\/1389203720666190722152415","article-title":"Virulence factors in Candida species","volume":"21","author":"Staniszewska","year":"2020","journal-title":"Curr. Protein Pept. SC."},{"key":"B46","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1002\/cjoc.200890073","article-title":"Synthesis and HIV-1 reverse transcriptase inhibitory activity of non-nucleoside phthalimide derivatives","volume":"26","author":"Ungwitayatorn","year":"2008","journal-title":"Chin. J. Chem."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.3390\/antibiotics10020215","article-title":"Baicalein inhibits Streptococcus mutans biofilms and dental caries-related virulence phenotypes","volume":"10","author":"Vijayakumar","year":"2021","journal-title":"Antibiotics"},{"key":"B48","doi-asserted-by":"publisher","first-page":"435","DOI":"10.2147\/IDR.S285690","article-title":"Evaluation of anti-biofilm capability of cordycepin against Candida albicans","volume":"14","author":"Wang","year":"2021","journal-title":"Infect. Drug Resist."},{"key":"B49","doi-asserted-by":"publisher","first-page":"467","DOI":"10.3934\/microbiol.2023025","article-title":"Biofilm: The invisible culprit in catheter-induced candidemia","volume":"9","author":"Wijaya","year":"2023","journal-title":"AIMS Microbiol."},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1016\/j.molstruc.2022.134688","article-title":"Phthalimide\/Naphthalimide containing 1,2,3-triazole hybrids: synthesis and antimicrobial evaluation","volume":"1276","author":"Yadav","year":"2023","journal-title":"J. Mol. Struct."},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/ardp.201700363","article-title":"Design, synthesis, biological evaluations, molecular docking, and in vivo studies of novel phthalimide analogs","volume":"351","author":"Zahran","year":"2018","journal-title":"Arch. Pharm. Chem. Life Sci."},{"key":"B52","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1038\/ncomms1685","article-title":"Sensing of mammalian IL-17A regulates fungal adaptation and virulence","volume":"3","author":"Zelante","year":"2012","journal-title":"Nat. Commun."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1414618\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,7,19]],"date-time":"2024-07-19T10:00:45Z","timestamp":1721383245000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2024.1414618\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,6,5]]},"references-count":52,"alternative-id":["10.3389\/fcimb.2024.1414618"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2024.1414618","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,6,5]]},"article-number":"1414618"}}