Abstract
Compounds 10a (IC50 110 pM) and 21 (IC50 40 pM) are the most potent inhibitors of Eimeria tenella cGMP-dependent protein kinase activity reported to date and are efficacious in the in vivo antiparasitic assay when administered to chickens at 12.5 and 6.25 ppm levels in the feed. However, both compounds are positive in the Ames microbial mutagenesis assay which precludes them from further development as antiprotozoal agents in the absence of negative lifetime rodent carcinogenicity studies.
MeSH terms
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Animal Feed
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Animals
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Antiprotozoal Agents / chemical synthesis*
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Antiprotozoal Agents / chemistry
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Antiprotozoal Agents / pharmacology
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Chickens
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Coccidiosis / drug therapy
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Cyclic GMP-Dependent Protein Kinases / antagonists & inhibitors*
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Eimeria tenella / drug effects*
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Eimeria tenella / enzymology
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Enzyme Inhibitors / chemical synthesis*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Imidazoles / chemical synthesis*
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Imidazoles / chemistry
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Imidazoles / pharmacology
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Male
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Molecular Structure
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Mutagenicity Tests
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Oocysts / drug effects
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Parasitic Sensitivity Tests
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Pyridines / chemical synthesis*
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Pyridines / chemistry
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Pyridines / pharmacology
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Rats
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Rats, Sprague-Dawley
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Stereoisomerism
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Structure-Activity Relationship
Substances
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Antiprotozoal Agents
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Enzyme Inhibitors
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Imidazoles
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Pyridines
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Cyclic GMP-Dependent Protein Kinases