Discovery of Novel Antigiardiasis Drug Candidates.

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TitleDiscovery of Novel Antigiardiasis Drug Candidates.
Publication TypeJournal Article
Year of Publication2014
AuthorsKulakova, L, Galkin, A, Chen, CZ, Southall, N, Marugan, JJ, Zheng, W, Herzberg, O
JournalAntimicrob Agents Chemother
Date Published2014 Sep 29
Abstract<p>Giardiasis is a severe intestinal parasitic disease, caused by Giardia lamblia, which inflicts many people in poor regions and the most common parasitic infection in the USA. Current standard-care drugs are associated with undesirable side effects, treatment failures, and increasing incidents of drug resistance. As follow-up to a high throughput screening of an approved drug library, which identified compounds lethal to G. lamblia trophozoites, we have determined the minimum lethal concentration of 28 drugs and advanced 10 of them to in vivo 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 Giardia activity. Three drugs, fumagillin, carbadox, and tioxidazole were identified. These compounds were also potent against metronidazole-resistant human G. lamblia isolates (assemblages A and B), as determined in in vitro assays. Of these three compounds, fumagillin is currently an orphan drug used within the European Union to treat microsporidiosis in immune compromised individuals, whereas carbadox and tioxidazole are used in veterinary medicine. A Dose-dependent study of fumagillin in the giardiasis mouse model revealed that the effective dose of fumagillin was ∼100-fold lower than the metronidazole dose. Therefore, fumagillin may be advanced to further studies as an alternative treatment of giardiasis when metronidazole fails.</p>
Alternate JournalAntimicrob. Agents Chemother.
PubMed ID25267663