{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T23:48:10Z","timestamp":1777506490403,"version":"3.51.4"},"reference-count":42,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/doi.org\/10.1128\/ASMCopyrightv2"},{"start":{"date-parts":[[2024,1,10]],"date-time":"2024-01-10T00:00:00Z","timestamp":1704844800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"funder":[{"name":"HHS | National Institutes of Health","award":["1KL2TR001444"],"award-info":[{"award-number":["1KL2TR001444"]}]},{"name":"HHS | National Institutes of Health","award":["DK120515"],"award-info":[{"award-number":["DK120515"]}]}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2024,1,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The intestinal parasites\n            <jats:italic>Giardia lamblia<\/jats:italic>\n            and\n            <jats:italic>Entamoeba histolytica<\/jats:italic>\n            are major causes of morbidity and mortality associated with diarrheal diseases. Metronidazole is the most common drug used to treat giardiasis and amebiasis. Despite its efficacy, treatment failures in giardiasis occur in up to 5%\u201340% of cases. Potential resistance of\n            <jats:italic>E. histolytica<\/jats:italic>\n            to metronidazole is an increasing concern. Therefore, it is critical to search for more effective drugs to treat giardiasis and amebiasis. We identified antigiardial and antiamebic activities of the rediscovered nitroimidazole compound, fexinidazole, and its sulfone and sulfoxide metabolites. Fexinidazole is equally active against\n            <jats:italic>E. histolytica<\/jats:italic>\n            and\n            <jats:italic>G. lamblia<\/jats:italic>\n            trophozoites, and both metabolites were 3- to 18-fold more active than the parent drug. Fexinidazole and its metabolites were also active against a metronidazole-resistant strain of\n            <jats:italic>G. lamblia<\/jats:italic>\n            .\n            <jats:italic>G. lamblia<\/jats:italic>\n            and\n            <jats:italic>E. histolytica<\/jats:italic>\n            cell extracts exhibited decreased residual nitroreductase activity when metabolites were used as substrates, indicating nitroreductase may be central to the mechanism of action of fexinidazole. In a cell invasion model, fexinidazole and its metabolites significantly reduced the invasiveness of\n            <jats:italic>E. histolytica<\/jats:italic>\n            trophozoites through basement membrane matrix. A q.d. oral dose of fexinidazole and its metabolites at 10 mg\/kg for 3 days reduced\n            <jats:italic>G. lamblia<\/jats:italic>\n            infection significantly in mice compared to control. The newly discovered antigiardial and antiamebic activities of fexinidazole, combined with its FDA-approval and inclusion in the WHO Model List of Essential Medicines for the treatment of human African trypanosomiasis, offer decreased risk and a shortened development timeline toward clinical use of fexinidazole for treatment of giardiasis or amebiasis.\n          <\/jats:p>","DOI":"10.1128\/aac.00731-23","type":"journal-article","created":{"date-parts":[[2023,12,8]],"date-time":"2023-12-08T14:00:20Z","timestamp":1702044020000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Antigiardial and antiamebic activities of fexinidazole and its metabolites: new drug leads for giardiasis and amebiasis"],"prefix":"10.1128","volume":"68","author":[{"given":"Jose Ignacio","family":"Escrig","sequence":"first","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yukiko","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alejandro Delgado","family":"Aznar","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lars","family":"Eckmann","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California San Diego , La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9294-3927","authenticated-orcid":true,"given":"Anjan","family":"Debnath","sequence":"additional","affiliation":[{"name":"Center for Discovery and Innovation in Parasitic Diseases, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California San Diego , La Jolla, California, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.3.447-475.2001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.14.1.114-128.2001"},{"key":"e_1_3_2_4_2","first-page":"15","article-title":"Giardiasis surveillance - United States, 2006-2008","volume":"59","author":"Yoder JS","year":"2010","unstructured":"Yoder JS , Harral C , Beach MJ , Centers for Disease Control and Prevention (CDC) . 2010. 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