{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,3]],"date-time":"2026-02-03T16:17:03Z","timestamp":1770135423867,"version":"3.49.0"},"reference-count":53,"publisher":"American Society for Microbiology","issue":"9","license":[{"start":{"date-parts":[[2013,9,1]],"date-time":"2013-09-01T00:00:00Z","timestamp":1377993600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2013,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            As eukaryotes, fungi possess relatively few molecules sufficiently unique from mammalian cell components to be used as drug targets. Consequently, most current antifungals have significant host cell toxicity. Primary fungal pathogens (e.g.,\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>\n            ) are of particular concern, as few antifungals are effective in treating them. To identify additional antifungal candidates for the treatment of histoplasmosis, we developed a high-throughput platform for monitoring\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>\n            growth and employed it in a phenotypic screen of 3,600 commercially available compounds. Seven hit compounds that inhibited\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>\n            yeast growth were identified. Compound 41F5 has fungistatic activity against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>\n            yeast at micromolar concentrations, with a 50% inhibitory concentration (IC\n            <jats:sub>50<\/jats:sub>\n            ) of 0.87 \u03bcM, and has the greatest selectivity for yeast (at least 62-fold) relative to host cells. Structurally, 41F5 consists of an aminothiazole core with an alicyclic substituent at the 2-position and an aromatic substituent at the 5-position. 41F5 inhibits\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>\n            growth in liquid culture and similarly inhibits yeast cells within macrophages, the actual host environment of this fungal pathogen during infection. Importantly, 41F5 protects infected host cells from\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>\n            -induced macrophage death, making this aminothiazole hit compound an excellent candidate for development as an antifungal for\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Histoplasma<\/jats:named-content>\n            infections.\n          <\/jats:p>","DOI":"10.1128\/aac.00459-13","type":"journal-article","created":{"date-parts":[[2013,7,2]],"date-time":"2013-07-02T01:07:13Z","timestamp":1372727233000},"page":"4349-4359","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":24,"title":["Identification of an Aminothiazole with Antifungal Activity against Intracellular Histoplasma capsulatum"],"prefix":"10.1128","volume":"57","author":[{"given":"Jessica A.","family":"Edwards","sequence":"first","affiliation":[{"name":"Department of Microbiology and Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan M.","family":"Kemski","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chad A.","family":"Rappleye","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Department of Microbial Infection and Immunity, Ohio State University, Columbus, Ohio, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1524-4733.2002.51108.x"},{"key":"e_1_3_2_3_2","first-page":"377","article-title":"Aqueous pores created in thin lipid membranes by the polyene antibiotics nystatin and amphotericin B","volume":"2","author":"Finkelstein A","year":"1973","unstructured":"FinkelsteinAHolzR. 1973. 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