{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T23:03:21Z","timestamp":1784588601877,"version":"3.55.0"},"reference-count":54,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T00:00:00Z","timestamp":1703721600000},"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>Candidal infections, particularly vulvovaginal candidiasis (VVC), necessitate effective therapeutic interventions in clinical settings owing to their intricate clinical nature and elusive understanding of their etiological mechanisms. Given the challenges in developing effective antifungal therapies, the strategy of repurposing existing pharmaceuticals has emerged as a promising approach to combat drug-resistant fungi. In this regard, the current study investigates molecular insights on the anti-candidal efficacy of a well-proven anticancer small molecule -3-bromopyruvate (3BP) against three clinically significant VVC causing <jats:italic>Candida<\/jats:italic> species <jats:italic>viz<\/jats:italic>., <jats:italic>C<\/jats:italic>. <jats:italic>albicans<\/jats:italic>, <jats:italic>C<\/jats:italic>. <jats:italic>tropicalis<\/jats:italic> and <jats:italic>C<\/jats:italic>. <jats:italic>glabrata<\/jats:italic>. Furthermore, the study validates 3BP\u2019s therapeutic application by developing it as a vaginal cream for the treatment of VVC. 3BP exhibited phenomenal antifungal efficacy (killing &gt;99%) with minimum inhibitory concentrations (MIC) and minimum fungicidal concentrations (MFC) of 256 \u03bcg\/mL against all tested <jats:italic>Candida<\/jats:italic> spp. Time killing kinetics experiment revealed 20 min as the minimum time required for 3BP at 2XMIC to achieve complete-killing (99.9%) in all <jats:italic>Candida<\/jats:italic> strains. Moreover, the ergosterol or sorbitol experiment explicated that the antifungal activity of 3BP does not stem from targeting the cell wall or the membrane component ergosterol. Instead, 3BP was observed to instigate a sequence of pre-apoptotic cascade events, such as phosphatidylserine (PS) externalization, nuclear condensation and ROS accumulations, as evidenced by PI, DAPI and DCFH-DA staining methods. Furthermore, 3BP demonstrated a remarkable efficacy in eradicating mature biofilms of <jats:italic>Candida<\/jats:italic> spp., achieving a maximum eradication level of 90%. Toxicity\/safety profiling in both <jats:italic>in vitro<\/jats:italic> erythrocyte lysis and <jats:italic>in vivo Galleria mellonella<\/jats:italic> survival assay authenticated the non-toxic nature of 3BP up to 512 \u03bcg\/mL. Finally, a vaginal cream formulated with 3BP was found to be effective in VVC-induced female mice model, as it significantly decreasing fungal load and protecting vaginal mucosa. Concomitantly, the present study serves as a clear demonstration of antifungal mechanistic action of anticancer drug -3BP, against <jats:italic>Candida<\/jats:italic> species. This finding holds significant potential for mitigating candidal infections, particularly VVC, within healthcare environments.<\/jats:p>","DOI":"10.1371\/journal.pone.0295922","type":"journal-article","created":{"date-parts":[[2023,12,28]],"date-time":"2023-12-28T18:28:22Z","timestamp":1703788102000},"page":"e0295922","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":8,"title":["ROS mediated anticandidal efficacy of 3-Bromopyruvate prevents vulvovaginal candidiasis in mice model"],"prefix":"10.1371","volume":"18","author":[{"given":"Ravi","family":"Jothi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong-Tshool","family":"Hong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Munkhtur","family":"Enkhtsatsral","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shunmugiah Karutha","family":"Pandian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5728-6837","authenticated-orcid":true,"given":"Shanmugaraj","family":"Gowrishankar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,12,28]]},"reference":[{"key":"pone.0295922.ref001","first-page":"1","article-title":"Metal sulfide nanoparticles based phytolectin scaffolds inhibit vulvovaginal candidiasis causing Candida albicans","author":"J. 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