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JAC Advance Access originally published online on May 18, 2004
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Journal of Antimicrobial Chemotherapy 2004 54(1):56-59; doi:10.1093/jac/dkh280
JAC vol.54 no.1 © The British Society for Antimicrobial Chemotherapy 2004; all rights reserved.

Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) as a target for anti-amoebic agents

Avelina Espinosa1,*, David Clark2 and Samuel L. Stanley, Jr1,3

Departments of 1 Molecular Microbiology, and 3 Medicine, Washington University School of Medicine, St Louis, MO 63110; 2 Department of Microbiology, Southern Illinois University, Carbondale, IL 62901, USA

* Correspondence address. University of Nebraska-Lincoln, Center for Biotechnology, N316 Beadle, PO Box 880660, Lincoln, NE 68588-0660, USA. Tel: +1-402-472-0500; Fax: +1-402-472-3139; Email: 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.

Keywords: bifunctional proteins , glycolytic pathways , eukaryotic parasites , cycloalkanols , alcohol dehydrogenase E


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