{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T22:07:45Z","timestamp":1780956465563,"version":"3.54.1"},"reference-count":62,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2014,7,1]],"date-time":"2014-07-01T00:00:00Z","timestamp":1404172800000},"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":[[2014,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Entamoeba histolytica<\/jats:named-content>\n            and\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            are anaerobic protozoan parasites that cause amebiasis and giardiasis, two of the most common diarrheal diseases worldwide. Current therapy relies on metronidazole, but resistance has been reported and the drug has significant adverse effects. Therefore, it is critical to search for effective, better-tolerated antiamebic and antigiardial drugs. We synthesized several examples of a recently reported class of Hsp90 inhibitors and evaluated these compounds as potential leads for antiparasitic chemotherapy. Several of these inhibitors showed strong\n            <jats:italic>in vitro<\/jats:italic>\n            activity against both\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. histolytica<\/jats:named-content>\n            and\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. The inhibitors were rescreened to discriminate between amebicidal and giardicidal activity and general cytotoxicity toward a mammalian cell line. No mammalian cytotoxicity was found at &gt;100 \u03bcM for 48 h for any of the inhibitors. To understand the mechanism of action, a competitive binding assay was performed using the fluorescent ATP analogue bis-ANS (4,4\u2032-dianilino-1,1\u2032-binaphthyl-5,5\u2032-disulfonic acid dipotassium salt) and recombinant\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. histolytica<\/jats:named-content>\n            Hsp90 preincubated in both the presence and absence of Hsp90 inhibitors. There was significant reduction in fluorescence compared to the level in the control, suggesting that\n            <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">E. histolytica<\/jats:named-content>\n            Hsp90 is a selective target. The\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy and safety of one Hsp90 inhibitor in a mouse model of amebic colitis and giardiasis was demonstrated by significant inhibition of parasite growth at a single oral dose of 5 mg\/kg of body weight\/day for 7 days and 10 mg\/kg\/day for 3 days. Considering the results for\n            <jats:italic>in vitro<\/jats:italic>\n            activity and\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy, Hsp90 inhibitors represent a promising therapeutic option for amebiasis and giardiasis.\n          <\/jats:p>","DOI":"10.1128\/aac.02576-14","type":"journal-article","created":{"date-parts":[[2014,5,13]],"date-time":"2014-05-13T08:07:32Z","timestamp":1399968452000},"page":"4138-4144","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":39,"title":["Hsp90 Inhibitors as New Leads To Target Parasitic Diarrheal Diseases"],"prefix":"10.1128","volume":"58","author":[{"given":"Anjan","family":"Debnath","sequence":"first","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dea","family":"Shahinas","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Clifford","family":"Bryant","sequence":"additional","affiliation":[{"name":"Small Molecule Discovery Center, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Hirata","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Diego, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukiko","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Diego, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiri","family":"Gut","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam R.","family":"Renslo","sequence":"additional","affiliation":[{"name":"Small Molecule Discovery Center, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dylan R.","family":"Pillai","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, University of Calgary, Alberta, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Eckmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon L.","family":"Reed","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of California, San Diego, San Diego, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James H.","family":"McKerrow","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, University of California, San Francisco, San Francisco, California, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/8.2.228"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(03)12830-9"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.1.114-128.2001"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2334-5-72"},{"key":"e_1_3_2_6_2","first-page":"11","article-title":"Giardiasis surveillance\u2014United States, 2003-2005. 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