| Title: | New trifluoromethyl ketones as potent inhibitors of esterases: 19F NMR spectroscopy of transition state analog complexes and structure-activity relationships |
| Author(s): | Rosell G; Herrero S; Guerrero A; |
| Address: | "Department of Pharmacology and Therapeutic Chemistry, Faculty of Pharmacy, University of Barcelona, Spain" |
| Journal Title: | Biochem Biophys Res Commun |
| ISSN/ISBN: | 0006-291X (Print) 0006-291X (Linking) |
| Abstract: | "A variety of trifluoromethyl ketones (TFMKs) have been studied as inhibitors of the antennal esterases of the Egyptian armyworm Spodoptera littoralis. The chemicals behaved as tight slow-binding inhibitors, the beta-thio derivatives being the most potent ones, particularly 3-octylthio-1,1,1-trifluoropropan-2-one (OTFP) with an IC50 of 0.08 microM. Other TFMKs, containing a propenyl group at the non-polar end of the molecule as in the natural pheromone structure (compounds 4, 8 and 9), were also notably active. Correlation studies of inhibition with lipophilicity (log P) indicated that the optimum log P values for activity of the beta-thio compounds are in the range of 3.03-5.11, while a higher lipophilicity (range 5.37-5.89) was required among the devoid of sulfur ketones. 19F NMR studies, carried out with OTFP, showed that the inhibitor binds the enzyme in a reversible manner, forming an adduct (probably a hemiacetal) of tetrahedral geometry with the active site of the enzyme. To our knowledge, this is the first time that such a study on a natural esterase extract has been undertaken" |
| Keywords: | Acetone/*analogs & derivatives/chemistry/pharmacology Animals Enzyme Inhibitors/chemistry/*pharmacology Esterases/*antagonists & inhibitors Fluorine Insecta Magnetic Resonance Spectroscopy Male Structure-Activity Relationship; |
| Notes: | "MedlineRosell, G Herrero, S Guerrero, A eng Research Support, Non-U.S. Gov't 1996/09/04 Biochem Biophys Res Commun. 1996 Sep 4; 226(1):287-92. doi: 10.1006/bbrc.1996.1347" |
