title: Novel heteroaromatic organofluorine inhibitors of fructose-1,6-bisphosphatase.
abstract: A broad group of compounds including substituted pyrazoles, pyrroles, indoles, and carbazoles were screened to identify potential inhibitor lead compounds of fructose-1,6-bisphosphatase (FBPase). Best inhibitors are (1H-indol-1-yl)(4-(trifluoromethyl)phenyl)methanone, ethyl 3-(3,5-dimethyl-1H-pyrrol-2-yl)-4,4,4-trifluoro-3-hydroxybutanoate, 3,5-diphenyl-1-(3-(trifluoromethyl) phenyl)-1H-pyrazole, and ethyl 3,3,3-trifluoro-2-hydroxy-2-(1-methyl-1H-indol-3-yl)propanoate. The IC50 values (3.1, 4.8, 6.1, and 11.9 microM) were comparable to that of AMP, the natural inhibitor of murine FBPase (IC50 of 4.0 microM). Docking programs were utilized to interpret the experiments.
authors.affiliation: Department of Chemistry, University of Massachusetts, Boston, Massachusetts 02125, USA.
authors.forename: Aleksandra
authors.initials: A
authors.lastname: Rudnitskaya
authors.forename: Ken
authors.initials: K
authors.lastname: Huynh
authors.forename: Béla
authors.initials: B
authors.lastname: Török
authors.forename: Kimberly
authors.initials: K
authors.lastname: Stieglitz
mesh_terms: D000249:Adenosine Monophosphate / Q000378:metabolism; D000818:Animals; D003198:Computer Simulation; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D005461:Fluorine / Q000494:pharmacology*; D006597:Fructose-Bisphosphatase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D007211:Indoles / Q000494:pharmacology; D020128:Inhibitory Concentration 50; D051379:Mice; D011720:Pyrazoles / Q000494:pharmacology
chemical_list: D004791:Enzyme Inhibitors; D007211:Indoles; D011720:Pyrazoles; D005461:Fluorine; D000249:Adenosine Monophosphate; D006597:Fructose-Bisphosphatase