Abstract
In the present study, we carried out a structure-activity analysis in Trichomonas vaginalis of a series of adenosine and uridine analogues. The most potent compounds were found to be 2' and 3' modified adenosine analogues some of which are potent inhibitors of S-adenosylhomocysteine hydrolase. The 9-(2-deoxy-2-fluoro-β,D-arabinofuranosyl)adenine compound was more potent than metronidazole, a current FDA approved and commonly prescribed drug for treatment of trichomoniasis. Its IC(50) was 0.09 μM compared to 0.72 μM for metronidazole.
Copyright © 2012 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenosine / analogs & derivatives*
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Adenosine / chemical synthesis*
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Adenosine / pharmacology
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Adenosylhomocysteinase / antagonists & inhibitors*
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Adenosylhomocysteinase / metabolism
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Animals
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Antiprotozoal Agents / chemical synthesis*
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Antiprotozoal Agents / pharmacology
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CHO Cells
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Cell Culture Techniques
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Cell Survival / drug effects
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Cricetinae
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / pharmacology
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Humans
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Inhibitory Concentration 50
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Metronidazole / pharmacology
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Protozoan Proteins / antagonists & inhibitors*
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Protozoan Proteins / metabolism
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Structure-Activity Relationship
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Trichomonas vaginalis / drug effects*
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Trichomonas vaginalis / growth & development
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Uridine / analogs & derivatives
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Uridine / chemical synthesis*
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Uridine / pharmacology
Substances
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Antiprotozoal Agents
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Enzyme Inhibitors
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Protozoan Proteins
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Metronidazole
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Adenosylhomocysteinase
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Adenosine
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Uridine