JAC Advance Access published online on May 18, 2004
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkh280
© 2004 by The British Society for Antimicrobial Chemotherapy
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1 Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA
* To whom correspondence should be addressed. E-mail: mespinosa2{at}unlnotes.unl.edu.
Objectives: The current use of metronidazole as an anti-amoebic agent causes significant side-effects. The purpose of this study was to identify alternative compounds with which to treat amoebiasis. Methods: We tested the effects of cyclopropyl (CPC) and cyclobutyl (CBC) carbinols on the survival of Entamoeba histolytica trophozoites and on the enzymatic activities of E. histolytica alcohol dehydrogenase 2 (EhADH2), a crucial enzyme in the amoebic fermentation pathway. Results: At 72 h, the estimated 50% inhibitory concentrations of CPC and CBC were 38.9 and 11.2 µM, respectively. The EhADH2 alcohol and aldehyde dehydrogenase activities were inhibited by 1.82 µM CPC and 0.89 µM CBC in vitro. Conclusions: CPC and CBC are expected to be non-toxic to humans at the concentrations required to eliminate E. histolytica trophozoites. Similarities between EhADH2 and the Giardia lamblia AdhE enzyme indicate that CPC and CBC could be effective drugs for treatment of both amoebiasis and giardiasis.
Revised January 5, 2004
Accepted April 13, 2004
Original article
Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) as a target for anti-amoebic agents
2 Department of Microbiology, Southern Illinois University, Carbondale, IL 62901, USA
3 Department of Molecular Microbiology, Washington University School of Medicine, St Louis, MO 63110, USA; Department of Medicine, Washington University School of Medicine, St Louis, MO 63110, USA
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