Alkyl 2-arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates as new effective and selective inhibitors of carboxylesterase

• Published in: Doklady. Biochemistry and biophysics 2015-11, Vol.465 (1), p.381-385
• Main Authors: Boltneva, N. P., Makhaeva, G. F., Kovaleva, N. V., Lushchekina, S. V., Burgart, Ya. V., Shchegol’kov, E. V., Saloutin, V. I., Chupakhin, O. N.
• Format: Article
• Language: English
• Subjects: Animals; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biophysics and Molecular Biology; Chemical compounds; Cholinesterase Inhibitors - chemistry; Cholinesterase Inhibitors - pharmacology; Cholinesterases - chemistry; Cholinesterases - metabolism; Enzymes; Horses; Humans; Hydrazones - chemistry; Hydrazones - pharmacology; Life Sciences; Liver; Molecular Docking Simulation; Propionates - chemistry; Propionates - pharmacology; Swine
• ISSN: 1607-6729; 1608-3091
• DOI: 10.1134/S1607672915060101

A series of alkyl 2-Arylhydrazinylidene-3-oxo-3-polyfluoroalkylpropionates was synthesized and their inhibitory activity with respect to porcine liver carboxylesterase (CaE, EC 3.1.1.1), human erythrocyte acetylcholinesterase (AChE, EC 3.1.1.7), and horse serum butyrylcholinesterase (BChE, EC 3.1.1.8) was studied. The molecular docking method was used to study the binding mode of the compounds in the active site of CaE. It was found that compounds containing the trifluoromethyl group in the third position of carbonyl chain are highly effective and selective inhibitors of CaE with nanomolar IC 50 values, which agrees well with the results of molecular docking.