1. Oxidosqualene cyclase inhibitors as antimicrobial agents.
- Author
-
Hinshaw JC, Suh DY, Garnier P, Buckner FS, Eastman RT, Matsuda SP, Joubert BM, Coppens I, Joiner KA, Merali S, Nash TE, and Prestwich GD
- Subjects
- 3T3 Cells, Amines chemistry, Animals, Anti-Infective Agents chemistry, Antifungal Agents pharmacology, Antiprotozoal Agents pharmacology, CHO Cells, Combinatorial Chemistry Techniques methods, Cricetinae, Enzyme Inhibitors chemistry, Humans, Inhibitory Concentration 50, Leishmania mexicana drug effects, Leishmania mexicana growth & development, Leishmania mexicana metabolism, Mice, Microbial Sensitivity Tests, Phenols chemistry, Pneumocystis drug effects, Pneumocystis growth & development, Pneumocystis metabolism, Rats, Toxoplasma drug effects, Toxoplasma growth & development, Toxoplasma metabolism, Trypanosoma brucei gambiense drug effects, Trypanosoma brucei gambiense growth & development, Trypanosoma brucei gambiense metabolism, Trypanosoma cruzi drug effects, Trypanosoma cruzi growth & development, Trypanosoma cruzi metabolism, Amines pharmacology, Anti-Infective Agents pharmacology, Enzyme Inhibitors pharmacology, Intramolecular Transferases antagonists & inhibitors, Phenols pharmacology
- 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.
- Published
- 2003
- Full Text
- View/download PDF