{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,3]],"date-time":"2026-10-03T14:32:29Z","timestamp":1791037949063,"version":"4.1.0"},"reference-count":33,"publisher":"American Chemical Society (ACS)","issue":"1","license":[{"start":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T00:00:00Z","timestamp":1355356800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T00:00:00Z","timestamp":1355356800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T00:00:00Z","timestamp":1355356800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-045"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2013,1,10]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The sulfonylurea herbicides exert their activity by inhibiting plant acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway. It has previously been shown that if the gene for AHAS is deleted in Candida albicans, attenuation of virulence is achieved, suggesting AHAS as an antifungal drug target. Herein, we have cloned, expressed, and purified C. albicans AHAS and shown that several sulfonylureas are inhibitors of this enzyme and possess antifungal activity. The most potent of these compounds is ethyl 2-(N-((4-iodo-6-methoxypyrimidin-2-yl)carbamoyl)sulfamoyl)benzoate (10c), which has a Ki value of 3.8 nM for C. albicans AHAS and an MIC90 of 0.7 \u03bcg\/mL for this fungus in cell-based assays. For the sulfonylureas tested there was a strong correlation between inhibitory activity toward C. albicans AHAS and fungicidal activity, supporting the hypothesis that AHAS is the target for their inhibitory activity within the cell.<\/jats:p>","DOI":"10.1021\/jm301501k","type":"journal-article","created":{"date-parts":[[2012,12,13]],"date-time":"2012-12-13T10:57:18Z","timestamp":1355396238000},"page":"210-219","source":"Crossref","is-referenced-by-count":81,"title":["Sulfonylureas Have Antifungal\nActivity and Are Potent\nInhibitors of\n                    <i>Candida albicans<\/i>\n                    Acetohydroxyacid\nSynthase"],"prefix":"10.1021","volume":"56","author":[{"given":"Yu-Ting","family":"Lee","sequence":"first","affiliation":[{"name":"The University of Queensland , , Brisbane 4072, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chang-Jun","family":"Cui","sequence":"additional","affiliation":[{"name":"Nankai University State-Key Laboratory and Institute of Elemento-Organic Chemistry, , Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eve W. L.","family":"Chow","sequence":"additional","affiliation":[{"name":"The University of Queensland , , Brisbane 4072, Queensland, Australia"},{"name":"The University of Queensland , , Brisbane 4072, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nason","family":"Pue","sequence":"additional","affiliation":[{"name":"The University of Queensland , , Brisbane 4072, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thierry","family":"Lonhienne","sequence":"additional","affiliation":[{"name":"The University of Queensland , , Brisbane 4072, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian-Guo","family":"Wang","sequence":"additional","affiliation":[{"name":"Nankai University State-Key Laboratory and Institute of Elemento-Organic Chemistry, , Tianjin 300071, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James A.","family":"Fraser","sequence":"additional","affiliation":[{"name":"The University of Queensland , , Brisbane 4072, Queensland, Australia"},{"name":"The University of Queensland , , Brisbane 4072, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luke W.","family":"Guddat","sequence":"additional","affiliation":[{"name":"The University of Queensland , , Brisbane 4072, Queensland, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2012,12,13]]},"reference":[{"issue":"Suppl. 1","key":"2026081706081883300_cit1","doi-asserted-by":"crossref","first-page":"65","DOI":"10.2165\/11315530-000000000-00000","article-title":"Invasive fungal\ninfections: The challenge continues","volume":"69","author":"Gullo","year":"2009","journal-title":"Drugs"},{"issue":"4","key":"2026081706081883300_cit2","doi-asserted-by":"crossref","first-page":"499","DOI":"10.1128\/CMR.9.4.499","article-title":"Epidemiology of nosocomial fungal infections","volume":"9","author":"Fridkin","year":"1996","journal-title":"Clin. Microbiol. Rev."},{"issue":"8","key":"2026081706081883300_cit3","first-page":"44","article-title":"The fungus among us: An antifungal\nreview","volume":"45","author":"Owens","year":"2010","journal-title":"U.S. Pharm."},{"key":"2026081706081883300_cit4","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1099\/mic.0.26928-0","article-title":"Cryptococcus neoformans\n            Ilv2p confers\nresistance to sulfometuron methyl and is required for survival at\n37\u00b0C and in vivo","volume":"150","author":"Kingsbury","year":"2004","journal-title":"Microbiology"},{"key":"2026081706081883300_cit5","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1099\/mic.0.034348-0","article-title":"Cytocidal amino\nacid starvation of Saccharomyces\ncerevisiae and Candida albicans acetolactate synthase (ilv2\u0394) mutants is influenced by the\ncarbon source and rapamycin","volume":"156","author":"Kingsbury","year":"2010","journal-title":"Microbiology"},{"key":"2026081706081883300_cit6","doi-asserted-by":"crossref","first-page":"2008","DOI":"10.1016\/j.plaphy.2007.12.004","article-title":"Structure\nand mechanism of inhibition\nof plant acetohydroxyacid synthase","volume":"46","author":"Duggleby","year":"2008","journal-title":"Plant Physiol.\nBiochem."},{"key":"2026081706081883300_cit7","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1021\/bk-1984-0255.ch002","article-title":"New high potency\nherbicides","volume-title":"Pesticide Synthesis through\nRational Approaches","author":"Sauers","year":"1984"},{"issue":"4656","key":"2026081706081883300_cit8","doi-asserted-by":"crossref","first-page":"1443","DOI":"10.1126\/science.224.4656.1443","article-title":"Acetolactate synthase is the site of action of two\nsulfonylurea herbicides in higher plants","volume":"224","author":"Chaleff","year":"1984","journal-title":"Science"},{"issue":"Pt 3","key":"2026081706081883300_cit9","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1042\/bj3330765","article-title":"Herbicide-resistant\nforms of Arabidopsis\nthaliana acetohydroxyacid synthase: Characterization\nof the catalytic properties and sensitivity to inhibitors of four\ndefined mutants","volume":"333","author":"Chang","year":"1998","journal-title":"Biochem. J."},{"key":"2026081706081883300_cit10","first-page":"83","article-title":"Resistance\nto acetolactate synthase inhibiting herbicides","volume-title":"Herbicide Resistance in Plants: Biology and Biochemistry","author":"Saari","year":"1994"},{"key":"2026081706081883300_cit11","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1146\/annurev-arplant-042809-112119","article-title":"Evolution in action:\nPlants resistant to herbicides","volume":"61","author":"Powles","year":"2010","journal-title":"Annu. Rev. Plant\nBiol."},{"issue":"7","key":"2026081706081883300_cit12","doi-asserted-by":"crossref","first-page":"2330","DOI":"10.1021\/bi047980a","article-title":"Elucidating the\nspecificity of binding of sulfonylurea herbicides to acetohydroxyacid\nsynthase","volume":"44","author":"McCourt","year":"2005","journal-title":"Biochemistry"},{"issue":"13","key":"2026081706081883300_cit13","doi-asserted-by":"crossref","first-page":"2895","DOI":"10.1046\/j.1432-1033.2003.03671.x","article-title":"Systematic characterization\nof mutations in yeast acetohydroxyacid synthase. Interpretation of\nherbicide-resistance data","volume":"270","author":"Duggleby","year":"2003","journal-title":"Eur. J. Biochem."},{"key":"2026081706081883300_cit14","unstructured":"Pang\n              S. S.\n            \n          \n          Expression,\npurification, characterization and reconstitution of the catalytic\nand regulatory subunits of Saccharomyces cerevisiae acetohydroxyacid synthase. Ph.D. Thesis, The University\nof Queensland, Brisbane, Australia, 2000."},{"issue":"11","key":"2026081706081883300_cit15","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s10822-005-9028-9","article-title":"Structure-activity\nrelationships for a new family of sulfonylurea herbicides","volume":"19","author":"Wang","year":"2005","journal-title":"J. Comput.-Aided Mol. Des."},{"issue":"9","key":"2026081706081883300_cit16a","doi-asserted-by":"crossref","first-page":"7639","DOI":"10.1074\/jbc.M211648200","article-title":"Molecular\nbasis of sulfonylurea herbicide inhibition of acetohydroxyacid synthase","volume":"278","author":"Pang","year":"2003","journal-title":"J. Biol. 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Microbiol."},{"key":"2026081706081883300_cit29","volume-title":"Reference Method for Broth Dilution Antifungal Susceptibility Testing\nof Yeasts","year":"2002"},{"issue":"21","key":"2026081706081883300_cit30","doi-asserted-by":"crossref","first-page":"2947","DOI":"10.1093\/bioinformatics\/btm404","article-title":"Clustal\nW and Clustal X version 2.0","volume":"23","author":"Larkin","year":"2007","journal-title":"Bioinformatics"},{"issue":"1","key":"2026081706081883300_cit31","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1128\/JCM.37.1.141-145.1999","article-title":"Influence\nof incubation time, inoculum size, and glucose concentrations\non spectrophotometric endpoint determinations for amphotericin B,\nfluconazole and intraconazole","volume":"37","author":"Nguyen","year":"1999","journal-title":"J. Clin. Microbiol."}],"container-title":["Journal of Medicinal Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/jm301501k","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jmcmar\/article-pdf\/56\/1\/210\/16875824\/jm301501k.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jmcmar\/article-pdf\/56\/1\/210\/16875824\/jm301501k.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T10:14:28Z","timestamp":1786961668000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jmcmar\/article\/56\/1\/210\/1590209\/Sulfonylureas-Have-Antifungal-Activity-and-Are"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,12,13]]},"references-count":33,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2012,12,13]]},"published-print":{"date-parts":[[2013,1,10]]}},"URL":"https:\/\/doi.org\/10.1021\/jm301501k","relation":{},"ISSN":["0022-2623","1520-4804"],"issn-type":[{"value":"0022-2623","type":"print"},{"value":"1520-4804","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,12,13]]}}}