{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T03:49:20Z","timestamp":1793332160206,"version":"4.5.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:00:00Z","timestamp":1512432000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,12,5]],"date-time":"2017-12-05T00:00:00Z","timestamp":1512432000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The lack of new antifungal compounds with unique mechanisms of action is a concern for therapeutic management of patients. To identify inhibitors against human pathogenic fungi, we screened ~3000 compounds provided by the Developmental Therapeutics Program of NIH\/NCI against a panel of pathogenic fungi including <jats:italic>Candida<\/jats:italic> species, <jats:italic>Aspergillus fumigatus<\/jats:italic>, and <jats:italic>Cryptococcus neoformans<\/jats:italic>. NSC319726 (a thiosemicarbazone) had broad antifungal activity in the range of 0.1\u20132.0\u2009\u00b5g\/ml and was also inhibitory to fluconazole-resistant isolates of <jats:italic>Candida<\/jats:italic> species. Synergy was demonstrated with NSC319726 and azoles, as well as caspofungin. The inhibitory concentration 50% (IC<jats:sub>50<\/jats:sub>) of NSC319726 was 35\u2013800-fold higher than the Minimum Inhibitory Concentration 50% (MIC<jats:sub>50<\/jats:sub> values), which indicates low compound toxicity to human cells <jats:italic>in vitro<\/jats:italic>. Transcriptome analysis of treated and untreated <jats:italic>C. albicans<\/jats:italic> using Gene Ontology (GO) revealed a large cluster of down regulated genes that encode translational proteins, especially those with ribosome biogenesis functions. As NSC319726 was first shown to have anti-cancer activity, its affects against human pathogenic fungi establish NSC319726 as a repurposed, off-patent compound that has potential antifungal activity. The minimal <jats:italic>in vitro<\/jats:italic> toxicity of lead optimized NSC319726 and its reasonable inhibitory activity against pathogens suggest advancing this compound to <jats:italic>in vivo<\/jats:italic> toxicity testing and protection studies against candidiasis.<\/jats:p>","DOI":"10.1038\/s41598-017-17147-x","type":"journal-article","created":{"date-parts":[[2017,11,29]],"date-time":"2017-11-29T15:19:19Z","timestamp":1511968759000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Repurposing an inhibitor of ribosomal biogenesis with broad anti-fungal activity"],"prefix":"10.1038","volume":"7","author":[{"given":"Nuo","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dongmei","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuhan","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Killeen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Groutas","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard","family":"Calderone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,12,5]]},"reference":[{"key":"17147_CR1","doi-asserted-by":"publisher","first-page":"165rv113","DOI":"10.1126\/scitranslmed.3004404","volume":"4","author":"GD Brown","year":"2012","unstructured":"Brown, G. 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