Abstract
Small-molecule oxidosqualene cyclase (OSC) inhibitors were found to be effective in assays against cloned OSC-like enzymes from human pathogens. A combinatorial library was prepared and used to identify lead compounds that inhibit the growth of Trypanosoma cruzi, Leishmania mexicana amazonensis, and Pneumocystis carinii in culture. Selectivity for the microorganisms in preference to mammalian cells was observed.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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3T3 Cells
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Amines / chemistry
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Amines / pharmacology*
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Animals
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Anti-Infective Agents / chemistry
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Anti-Infective Agents / pharmacology*
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Antifungal Agents / pharmacology
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Antiprotozoal Agents / pharmacology
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CHO Cells
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Combinatorial Chemistry Techniques / methods
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Cricetinae
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology*
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Humans
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Inhibitory Concentration 50
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Intramolecular Transferases / antagonists & inhibitors*
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Leishmania mexicana / drug effects
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Leishmania mexicana / growth & development
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Leishmania mexicana / metabolism
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Mice
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Microbial Sensitivity Tests
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Phenols / chemistry
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Phenols / pharmacology*
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Pneumocystis / drug effects
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Pneumocystis / growth & development
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Pneumocystis / metabolism
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Rats
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Toxoplasma / drug effects
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Toxoplasma / growth & development
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Toxoplasma / metabolism
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Trypanosoma brucei gambiense / drug effects
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Trypanosoma brucei gambiense / growth & development
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Trypanosoma brucei gambiense / metabolism
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Trypanosoma cruzi / drug effects
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Trypanosoma cruzi / growth & development
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Trypanosoma cruzi / metabolism
Substances
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Amines
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Anti-Infective Agents
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Antifungal Agents
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Antiprotozoal Agents
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Enzyme Inhibitors
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Phenols
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Intramolecular Transferases
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lanosterol synthase