{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:31:54Z","timestamp":1787016714931,"version":"build-2736575974"},"reference-count":50,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2014,12,1]],"date-time":"2014-12-01T00:00:00Z","timestamp":1417392000000},"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":[[2014,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Giardiasis is a severe intestinal parasitic disease caused by\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Giardia lamblia<\/jats:named-content>\n                    , which inflicts many people in poor regions and is the most common parasitic infection in the United States. Current standard care drugs are associated with undesirable side effects, treatment failures, and an increasing incidence of drug resistance. As follow-up to a high-throughput screening of an approved drug library, which identified compounds lethal to\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">G. lamblia<\/jats:named-content>\n                    trophozoites, we have determined the minimum lethal concentrations of 28 drugs and advanced 10 of them to\n                    <jats:italic>in vivo<\/jats:italic>\n                    studies in mice. The results were compared to treatment with the standard care drug, metronidazole, in order to identify drugs with equal or better anti-\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Giardia<\/jats:named-content>\n                    activities. Three drugs, fumagillin, carbadox, and tioxidazole, were identified. These compounds were also potent against metronidazole-resistant human\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">G. lamblia<\/jats:named-content>\n                    isolates (assemblages A and B), as determined in\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays. Of these three compounds, fumagillin is currently an orphan drug used within the European Union to treat microsporidiosis in immunocompromised individuals, whereas carbadox and tioxidazole are used in veterinary medicine. A dose-dependent study of fumagillin in a giardiasis mouse model revealed that the effective dose of fumagillin was \u223c100-fold lower than the metronidazole dose. Therefore, fumagillin may be advanced to further studies as an alternative treatment for giardiasis when metronidazole fails.\n                  <\/jats:p>","DOI":"10.1128\/aac.03834-14","type":"journal-article","created":{"date-parts":[[2014,9,29]],"date-time":"2014-09-29T22:09:54Z","timestamp":1412028594000},"page":"7303-7311","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Discovery of Novel Antigiardiasis Drug Candidates"],"prefix":"10.1128","volume":"58","author":[{"given":"Liudmila","family":"Kulakova","sequence":"first","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey","family":"Galkin","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine Z.","family":"Chen","sequence":"additional","affiliation":[{"name":"Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Noel","family":"Southall","sequence":"additional","affiliation":[{"name":"Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan J.","family":"Marugan","sequence":"additional","affiliation":[{"name":"Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Zheng","sequence":"additional","affiliation":[{"name":"Division of Preclinical Innovation, National Center for Advancing Translational Sciences, National Institutes of Health, Bethesda, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Osnat","family":"Herzberg","sequence":"additional","affiliation":[{"name":"Institute for Bioscience and Biotechnology Research, University of Maryland, Rockville, Maryland, USA"},{"name":"Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2006.02.015"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1185\/030079906X132497"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1179\/136485908X267894"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/46.5.819"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.1.150-164.2001"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1080\/02813430802602393"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00618-10"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/152.1.64"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(83)90120-7"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1016\/0035-9203(92)90095-T"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01675-12"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.62.8.3583-3585.1994"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.553123"},{"key":"e_1_3_2_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.6.1488"},{"key":"e_1_3_2_16_2","volume-title":"Dietary reference intakes: proposed definition and plan for review of dietary antioxidants and related compounds","author":"Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference Intakes","year":"1998","unstructured":"Institute of Medicine Standing Committee on the Scientific Evaluation of Dietary Reference Intakes. 1998. 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