Entamoeba histolytica alcohol dehydrogenase 2 (EhADH2) as a target for anti-amoebic agents.
OBJECTIVE
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 microM, respectively. The EhADH2 alcohol and aldehyde dehydrogenase activities were inhibited by 1.82 microM CPC and 0.89 microM 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.
Espinosa
Avelina
A
Departments of Molecular Microbiology, and Medicine, Washington University School of Medicine, St Louis, MO 63110, USA. mespinosa2@unlnotes.unl.edu
Clark
David
D
Stanley
Samuel L
SL
D000426:Alcohol Dehydrogenase / Q000037:antagonists & inhibitors*; D000444:Aldehyde Dehydrogenase / Q000037:antagonists & inhibitors; D000818:Animals; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D003503:Cyclobutanes / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D004748:Entamoeba histolytica / Q000187:drug effects* / Q000201:enzymology* / Q000254:growth & development; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D000432:Methanol / Q000031:analogs & derivatives / Q000494:pharmacology; D011994:Recombinant Proteins
D000981:Antiprotozoal Agents; D003503:Cyclobutanes; D003521:Cyclopropanes; D004791:Enzyme Inhibitors; D011994:Recombinant Proteins; C490696:cyclobutylcarbinol; C490695:cyclopropylcarbinol; D000426:Alcohol Dehydrogenase; D000444:Aldehyde Dehydrogenase; D000432:Methanol