Oxidosqualene cyclase inhibitors as antimicrobial agents.
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.
D016475:3T3 Cells; D000588:Amines / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology; D000981:Antiprotozoal Agents / Q000494:pharmacology; D016466:CHO Cells; D020650:Combinatorial Chemistry Techniques / Q000379:methods; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D019751:Intramolecular Transferases / Q000037:antagonists & inhibitors*; D007894:Leishmania mexicana / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008826:Microbial Sensitivity Tests; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology*; D011010:Pneumocystis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D051381:Rats; D014122:Toxoplasma / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D014347:Trypanosoma brucei gambiense / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D014349:Trypanosoma cruzi / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism
D000588:Amines; D000890:Anti-Infective Agents; D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D004791:Enzyme Inhibitors; D010636:Phenols; D019751:Intramolecular Transferases; C021924:lanosterol synthase