{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T11:51:25Z","timestamp":1791287485226,"version":"4.1.0"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"5","license":[{"start":{"date-parts":[[2014,5,1]],"date-time":"2014-05-01T00:00:00Z","timestamp":1398902400000},"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":[[2014,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The apicomplexan parasites\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptosporidium parvum<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptosporidium hominis<\/jats:named-content>\n            are major etiologic agents of human cryptosporidiosis. The infection is typically self-limited in immunocompetent adults, but it can cause chronic fulminant diarrhea in immunocompromised patients and malnutrition and stunting in children. Nitazoxanide, the current standard of care for cryptosporidiosis, is only partially efficacious for children and is no more effective than a placebo for AIDS patients. Unfortunately, financial obstacles to drug discovery for diseases that disproportionately affect low-income countries and technical limitations associated with studies of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Cryptosporidium<\/jats:named-content>\n            biology impede the development of better drugs for treating cryptosporidiosis. Using a cell-based high-throughput screen, we queried the Medicines for Malaria Venture (MMV) Open Access Malaria Box for activity against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parvum<\/jats:named-content>\n            . We identified 3 novel chemical series derived from the quinolin-8-ol, allopurinol-based, and 2,4-diamino-quinazoline chemical scaffolds that exhibited submicromolar potency against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parvum<\/jats:named-content>\n            . Potency was conserved in a subset of compounds from each scaffold with varied physicochemical properties, and two of the scaffolds identified exhibit more rapid inhibition of\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parvum<\/jats:named-content>\n            growth than nitazoxanide, making them excellent candidates for further development. The 2,4-diamino-quinazoline and allopurinol-based compounds were also potent growth inhibitors of the related apicomplexan parasite\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Toxoplasma gondii<\/jats:named-content>\n            , and a good correlation was observed in the relative activities of the compounds in the allopurinol-based series against\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">T. gondii<\/jats:named-content>\n            and\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parvum<\/jats:named-content>\n            . Taken together, these data illustrate the utility of the Open Access Malaria Box as a source of both potential leads for drug development and chemical probes to elucidate basic biological processes in\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">C. parvum<\/jats:named-content>\n            and other apicomplexan parasites.\n          <\/jats:p>","DOI":"10.1128\/aac.02641-13","type":"journal-article","created":{"date-parts":[[2014,2,25]],"date-time":"2014-02-25T02:39:52Z","timestamp":1393295992000},"page":"2731-2739","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":76,"title":["Identification of Cryptosporidium parvum Active Chemical Series by Repurposing the Open Access Malaria Box"],"prefix":"10.1128","volume":"58","author":[{"given":"Kovi","family":"Bessoff","sequence":"first","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Spangenberg","sequence":"additional","affiliation":[{"name":"Medicines for Malaria Venture, Geneva, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenna E.","family":"Foderaro","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rajiv S.","family":"Jumani","sequence":"additional","affiliation":[{"name":"Cell, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, Vermont, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary E.","family":"Ward","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA"},{"name":"Cell, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, Vermont, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher D.","family":"Huston","sequence":"additional","affiliation":[{"name":"Department of Microbiology and Molecular Genetics, University of Vermont, Burlington, Vermont, USA"},{"name":"Cell, Molecular, and Biomedical Sciences Graduate Program, University of Vermont, Burlington, Vermont, USA"},{"name":"Department of Medicine, University of Vermont, Burlington, Vermont, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.17.1.72-97.2004"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra013170"},{"key":"e_1_3_3_4_2","first-page":"1","article-title":"Cryptosporidiosis surveillance\u2013United States, 2009\u20132010","volume":"61","author":"Yoder JS","year":"2012","unstructured":"YoderJSWallaceRMCollierSABeachMJHlavsaMC. 2012. 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