Treatment of Diarrhea Caused byGiardia intestinalisandEntamoeba histolyticaorE. dispar:A Randomized, Double‐Blind, Placebo‐Controlled Study of Nitazoxanide

Rossignol, Jean‐François; Ayoub, Ayman; Ayers, Marc S.

doi:10.1086/322038

Cited by 145 publications

(75 citation statements)

References 12 publications

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“…In addition, follow-up treatment with a second drug, such as paromomycin, is recommended for amebiasis to prevent prolonged retention and excretion of cysts (20). Newer metronidazole derivatives, such as tinidazole (21) and nitazoxanide, a nitrothiazoly-salicylamide derivative (22), have fewer side effects and shorter treatment courses. Other drugs, such as furazolidone, albendazole, and paromomycin, are used for giardiasis to a lesser extent, with similar or lower success rates.…”

Section: T He Protozoan Intestinal Parasites Entamoeba Histolytica Andmentioning

confidence: 99%

Hsp90 Inhibitors as New Leads To Target Parasitic Diarrheal Diseases

Debnath

Shahinas

Bryant

et al. 2014

Antimicrob Agents Chemother

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Entamoeba histolytica and Giardia lamblia 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 in vitro activity against both E. histolytica and G. lamblia 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 >100 M 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=-dianilino-1,1=-binaphthyl-5,5=-disulfonic acid dipotassium salt) and recombinant E. histolytica 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 E. histolytica Hsp90 is a selective target. The in vivo 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 in vitro activity and in vivo efficacy, Hsp90 inhibitors represent a promising therapeutic option for amebiasis and giardiasis.

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Section: T He Protozoan Intestinal Parasites Entamoeba Histolytica Andmentioning

confidence: 99%

Hsp90 Inhibitors as New Leads To Target Parasitic Diarrheal Diseases

Debnath

Shahinas

Bryant

et al. 2014

Antimicrob Agents Chemother

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“…The first-line drugs for invasive amebiasis and giardiasis chemotherapy are nitroimidazoles, with the prototype, metronidazole, being the most common drug used worldwide. 13 Newer metronidazole derivatives such as tinidazole 14 and nitazoxanide, a nitrothiazoly-salicylamide derivative, 15 have fewer side-effects and are shorter treatment courses. Other drugs, such as furazolidone, albendazole and paromomycin are used for giardiasis to a lesser extent with similar and/or lower success rates.…”

Section: Killing Three Parasites With One Drugmentioning

confidence: 99%

Reprofiled drug targets ancient protozoans

2013

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“…Herein we document the anti-influenza activity of nitazoxanide (NTZ), a thiazolide anti-infective licensed in the United States (Alinia; Romark Laboratories, Tampa, FL) for treating enteritis caused by Cryptosporidium parvum and Giardia lamblia in children and adults (12)(13)(14), its active circulating metabolite tizoxanide (2-hydroxy-N-(5-nitro-2-thiazolyl)benzamide) (TIZ) (see Fig. 1A), and second generation thiazolides.…”

mentioning

confidence: 99%

Thiazolides, a New Class of Anti-influenza Molecules Targeting Viral Hemagglutinin at the Post-translational Level

Rossignol

Frazia

Chiappa

et al. 2009

Journal of Biological Chemistry

220

253

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The emergence of highly contagious influenza A virus strains, such as the new H1N1 swine influenza, represents a serious threat to global human health. Efforts to control emerging influenza strains focus on surveillance and early diagnosis, as well as development of effective vaccines and novel antiviral drugs. Herein we document the anti-influenza activity of the anti-infective drug nitazoxanide and its active circulating-metabolite tizoxanide and describe a class of second generation thiazolides effective against influenza A virus. Thiazolides inhibit the replication of H1N1 and different other strains of influenza A virus by a novel mechanism: they act at post-translational level by selectively blocking the maturation of the viral hemagglutinin at a stage preceding resistance to endoglycosidase H digestion, thus impairing hemagglutinin intracellular trafficking and insertion into the host plasma membrane, a key step for correct assembly and exit of the virus from the host cell. Targeting the maturation of the viral glycoprotein offers the opportunity to disrupt the production of infectious viral particles attacking the pathogen at a level different from the currently available anti-influenza drugs. The results indicate that thiazolides may represent a new class of antiviral drugs effective against influenza A infection.

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Treatment of Diarrhea Caused byGiardia intestinalisandEntamoeba histolyticaorE. dispar:A Randomized, Double‐Blind, Placebo‐Controlled Study of Nitazoxanide

Cited by 145 publications

References 12 publications

Hsp90 Inhibitors as New Leads To Target Parasitic Diarrheal Diseases

Hsp90 Inhibitors as New Leads To Target Parasitic Diarrheal Diseases

Reprofiled drug targets ancient protozoans

Thiazolides, a New Class of Anti-influenza Molecules Targeting Viral Hemagglutinin at the Post-translational Level

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