{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,28]],"date-time":"2025-12-28T07:53:04Z","timestamp":1766908384354,"version":"3.40.5"},"reference-count":30,"publisher":"Public Library of Science (PLoS)","issue":"6","license":[{"start":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T00:00:00Z","timestamp":1687305600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p><jats:italic>Candida auris<\/jats:italic>, the youngest <jats:italic>Candida<\/jats:italic> species, is known to cause candidiasis and candidemia in humans and has been related to several hospital outbreaks. Moreover, <jats:italic>Candida auris<\/jats:italic> infections are largely resistant to the antifungal drugs currently in clinical use, necessitating the development of novel medications and approaches to treat such infections. Following up on our previous studies that demonstrated eugenol tosylate congeners (ETCs) to have antifungal activity, several ETCs (C1-C6) were synthesized to find a lead molecule with the requisite antifungal activity against <jats:italic>C<\/jats:italic>. <jats:italic>auris<\/jats:italic>. Preliminary tests, including broth microdilution and the MUSE cell viability assay, identified C5 as the most active derivative, with a MIC value of 0.98 g\/mL against all strains tested. Cell count and viability assays further validated the fungicidal activity of C5. Apoptotic indicators, such as phosphatidylserine externalization, DNA fragmentation, mitochondrial depolarization, decreased cytochrome c and oxidase activity and cell death confirmed that C5 caused apoptosis in <jats:italic>C<\/jats:italic>. <jats:italic>auris<\/jats:italic> isolates. The low cytotoxicity of C5 further confirmed the safety of using this derivative in future studies. To support the conclusions drawn in this investigation, additional <jats:italic>in vivo<\/jats:italic> experiments demonstrating the antifungal activity of this lead compound in animal models will be needed.<\/jats:p>","DOI":"10.1371\/journal.pone.0285473","type":"journal-article","created":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T20:06:58Z","timestamp":1687378018000},"page":"e0285473","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["Cellular apoptosis and cell cycle arrest as potential therapeutic targets for eugenol derivatives in Candida auris"],"prefix":"10.1371","volume":"18","author":[{"given":"Hammad","family":"Alam","sequence":"first","affiliation":[]},{"given":"Vartika","family":"Srivastava","sequence":"additional","affiliation":[]},{"given":"Windy","family":"Sekgele","sequence":"additional","affiliation":[]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1838-1337","authenticated-orcid":true,"given":"Mohmmad Younus","family":"Wani","sequence":"additional","affiliation":[]},{"given":"Abdullah Saad","family":"Al-Bogami","sequence":"additional","affiliation":[]},{"given":"Julitha","family":"Molepo","sequence":"additional","affiliation":[]},{"given":"Aijaz","family":"Ahmad","sequence":"additional","affiliation":[]}],"member":"340","published-online":{"date-parts":[[2023,6,21]]},"reference":[{"issue":"1","key":"pone.0285473.ref001","doi-asserted-by":"crossref","first-page":"41","DOI":"10.1111\/j.1348-0421.2008.00083.x","article-title":"Candida auris sp. nov., a novel ascomycetous yeast isolated from the external ear canal of an inpatient in a Japanese hospital","volume":"53","author":"K. Satoh","year":"2009","journal-title":"Microbiol. Immunol"},{"issue":"3","key":"pone.0285473.ref002","doi-asserted-by":"crossref","first-page":"203","DOI":"10.1016\/j.tim.2022.01.010","article-title":"New tools for the new bug Candida auris","volume":"30","author":"A. Lorenz","year":"2022","journal-title":"Trends Microbiol"},{"key":"pone.0285473.ref003","doi-asserted-by":"crossref","first-page":"84","DOI":"10.1016\/j.mib.2019.05.008","article-title":"Global epidemiology of emerging Candida auris","volume":"52","author":"J. Rhodes","year":"2019","journal-title":"Curr. Opin. Microbiol"},{"issue":"10","key":"pone.0285473.ref004","doi-asserted-by":"crossref","first-page":"e1008921","DOI":"10.1371\/journal.ppat.1008921","article-title":"Candida auris: Epidemiology, biology, antifungal resistance, and virulence","volume":"16","author":"H. Du","year":"2020","journal-title":"PLoS pathogens"},{"issue":"1","key":"pone.0285473.ref005","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1080\/21505594.2022.2026037","article-title":"From environmental adaptation to host survival: Attributes that mediate pathogenicity of Candida auris.","volume":"13","author":"S. Allert","year":"2022","journal-title":"Virulence"},{"journal-title":"development, and public health action\u2019 was published by the World Health Organization on Tuesday","year":"2022","author":"WHO fungal priority pathogens list to guide research","key":"pone.0285473.ref006"},{"key":"pone.0285473.ref007","doi-asserted-by":"crossref","first-page":"i60","DOI":"10.1093\/jac\/dkx450","article-title":"Echinocandin prophylaxis in patients undergoing haematopoietic cell transplantation and other treatments for haematological malignancies","volume":"73","author":"D. J. Epstein","year":"2018","journal-title":"J. Antimicrob. Chemotherapy"},{"issue":"3","key":"pone.0285473.ref008","doi-asserted-by":"crossref","first-page":"185","DOI":"10.3390\/jof6030185","article-title":"Echinocandins as biotechnological tools for treating candida auris infections","volume":"6","author":"E. D. S. C\u00e2ndido","year":"2020","journal-title":"J Fungi"},{"issue":"1","key":"pone.0285473.ref009","doi-asserted-by":"crossref","first-page":"31","DOI":"10.3390\/jof7010031","article-title":"Characteristics, risk factors, and survival analysis of Candida auris cases: results of one-year national surveillance data from Oman","volume":"7","author":"A. Al-Rashdi","year":"2021","journal-title":"J Fungi"},{"issue":"4","key":"pone.0285473.ref010","doi-asserted-by":"crossref","first-page":"e00578","DOI":"10.1002\/mbo3.578","article-title":"Candida auris: A systematic review and meta\u2010analysis of current updates on an emerging multidrug\u2010resistant pathogen","volume":"7","author":"J. Osei Sekyere","year":"2018","journal-title":"Microbiol open"},{"key":"pone.0285473.ref011","article-title":"Candida auris,\u201d in Stat Pearls, Stat Pearls Publishing","author":"A. Sikora","year":"2022","journal-title":"Treasure Island (FL)"},{"issue":"11","key":"pone.0285473.ref012","doi-asserted-by":"crossref","first-page":"900","DOI":"10.3390\/jof7110900","article-title":"Recent approaches towards control of fungal diseases in plants: An updated review","volume":"7","author":"N. A. El-Baky","year":"2021","journal-title":"Journal of Fungi"},{"key":"pone.0285473.ref013","doi-asserted-by":"crossref","first-page":"3671","DOI":"10.3390\/ijms22073671","article-title":"Biological Properties, and prospects for the application of eugenol, A review","volume":"22","author":"M. Ulanowska","year":"2021","journal-title":"Int. J. Mol. Sci"},{"key":"pone.0285473.ref014","first-page":"1","article-title":"Inhibitory effect of novel Eugenol Tosylate Congeners on pathogenicity of Candida albicans","volume":"20","author":"S. A. Lone","year":"2020","journal-title":"BMC Complement Altern Med"},{"issue":"12","key":"pone.0285473.ref015","doi-asserted-by":"crossref","first-page":"e0145053","DOI":"10.1371\/journal.pone.0145053","article-title":"Synergistic interactions of eugenol-tosylate and its congeners with fluconazole against Candida albicans","volume":"10","author":"A. Ahmad","year":"2015","journal-title":"Plos one"},{"key":"pone.0285473.ref016","first-page":"13","article-title":"Eugenol: A novel therapeutic agent for the inhibition of Candida species infection. Front","author":"M. Didehdar","year":"2022","journal-title":"Pharmacol."},{"key":"pone.0285473.ref017","first-page":"1055","article-title":"The multiple faces of eugenol. A versatile starting material and building block for organic and bio-organic synthesis and a convenient precursor toward bio-based fine chemicals","volume":"26","author":"T. S. Kaufman","year":"2015","journal-title":"J. Braz. Chem. Soc"},{"issue":"1","key":"pone.0285473.ref018","first-page":"1","article-title":"Cellular apoptosis and necrosis as therapeutic targets for novel eugenol tosylate congeners against Candida albicans","volume":"10","author":"S. A. Lone","year":"2020","journal-title":"Sci. Rep"},{"issue":"1","key":"pone.0285473.ref019","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1016\/j.patbio.2010.07.020","article-title":"Comparison of the Sensititre YeastOne\u00ae dilution method with the Clinical Laboratory Standards Institute (CLSI) M27-A3 microbroth dilution reference method for determining MIC of eight antifungal agents on 102 yeast strains","volume":"59","author":"S. Bertout","year":"2011","journal-title":"Pathol. Biol"},{"key":"pone.0285473.ref020","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.biocel.2016.09.008","article-title":"Silibinin triggers yeast apoptosis related to mitochondrial Ca2+ influx in Candida albicans","volume":"80","author":"DG Yun","year":"2016","journal-title":"Int J Biochem Cell Biol"},{"key":"pone.0285473.ref021","article-title":"Pharmacological properties and health benefits of eugenol: A comprehensive review.","author":"M. F. Nisar","year":"2021","journal-title":"Oxidative Medicine and Cellular Longevity, 2021"},{"key":"pone.0285473.ref022","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1590\/S1982-56762010000300001","article-title":"Antifungal activity of eugenol against Botrytis cinerea","volume":"35","author":"C. Wang","year":"2010","journal-title":"Tropical Plant Pathology"},{"issue":"14","key":"pone.0285473.ref023","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.2174\/1381612826666200403120448","article-title":"Synthesis of Eugenol Derivatives and Evaluation of their Antifungal Activity Against Fusarium solani f. sp","volume":"26","author":"S. C. Maximino","year":"2020","journal-title":"piperis. Current Pharmaceutical Design"},{"key":"pone.0285473.ref024","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.mib.2022.102208","article-title":"The molecular and genetic basis of antifungal resistance in the emerging fungal pathogen Candida auris","volume":"70","author":"J. M. Rybak","year":"2022","journal-title":"Curr. Opin. Microbiol"},{"issue":"21","key":"pone.0285473.ref025","first-page":"6387","article-title":"Clove essential oil (Syzygium aromaticum L","volume":"26","author":"J. N. Haro-Gonz\u00e1lez","year":"2021","journal-title":"Myrtaceae): Extraction, chemical composition, food applications, and essential bioactivity for human health. Molecules"},{"key":"pone.0285473.ref026","article-title":"Antifungal compounds against Candida infections from traditional Chinese medicine","author":"X. Liu","year":"2017","journal-title":"Biomed Res. Int. 2017"},{"key":"pone.0285473.ref027","first-page":"1","volume":"2013","author":"S. Y. Pan","year":"2013","journal-title":"New perspectives on how to discover drugs from herbal medicines: CAM\u2019s outstanding contribution to modern therapeutics eCAM"},{"key":"pone.0285473.ref028","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1016\/B978-0-12-386454-3.00242-6","volume-title":"Encyclopedia of Toxicology","author":"D. A. Brown","year":"2014"},{"issue":"1","key":"pone.0285473.ref029","doi-asserted-by":"crossref","first-page":"62","DOI":"10.3390\/jof7010062","article-title":"Facile bio-fabrication of Ag-Cu-Co trimetallic nanoparticles and its fungicidal activity against Candida auris","volume":"7","author":"M. R. Kamli","year":"2021","journal-title":"J Fungi"},{"key":"pone.0285473.ref030","first-page":"1","article-title":"Ethanolic extract of Caesalpinia bonduc seeds triggers yeast metacaspase-dependent apoptotic pathway mediated by mitochondrial dysfunction through enhanced production of calcium and reactive oxygen species (ROS) in Candida albicans","author":"S. Sasidharan","year":"2022","journal-title":"Front. Cell. Infect. Microbiol"}],"container-title":["PLOS ONE"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0285473","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,6,21]],"date-time":"2023-06-21T20:07:38Z","timestamp":1687378058000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0285473"}},"subtitle":[],"editor":[{"given":"Muhammad","family":"Yasir","sequence":"first","affiliation":[]}],"short-title":[],"issued":{"date-parts":[[2023,6,21]]},"references-count":30,"journal-issue":{"issue":"6","published-online":{"date-parts":[[2023,6,21]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0285473","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2023,6,21]]}}}