BROEDEL SE, RAULLI R, KRUEGER K, KHAN I, JOSHI A, KHAN S, DAWSON C, WALKER LA; Interscience Conference on Antimicrobial Agents and Chemotherapy.
Abstr Intersci Conf Antimicrob Agents Chemother Intersci Conf Antimicrob Agents Chemother. 2000 Sep 17-20; 40: 202.
Dorlin Pharmaceuticals, Inc., Baltimore, MD
Fatty acid synthase represents a potential new target for antifungal drug development. Toward identifying effective inhibitors, a multi-stepped mechanism-based screen was developed. The first step in the screen is a cell-free enzyme assay designed to identify inhibitors of FAS enzyme activity. The second tests are a susceptibility and rescue from susceptibility test. The latter test is used verify that the growth inhibition is due to inhibition of fatty acid biosynthesis in cultured cells. The bioassays were used to screen a natural product library composed of plant extracts. From 2,550 extracts, 15 extracts containing one or more compounds which inhibited FAS activity and exhibiting antifungal activity were identified. The active agents in one extract, from the plant Chlorophora tinctoriaI, were purified through a series of solvent extractions and chromatographic separations, and their structures elucidated. Eight structurally related compounds were identified. Five of the compounds were novel chemical entities and represent a new class of FAS inhibitors.KEYWORDS: Enzyme inhibitor; Fatty acids; Natural products
Publication Types:
Keywords:
- Antifungal Agents
- Biological Assay
- Enzyme Inhibitors
- Fatty Acid Synthetase Complex
- Fatty Acids
- Miconazole
- antagonists & inhibitors
- classification
Other ID:
UI: 102248117
From Meeting Abstracts