ABSTRACT
The three-component cyclization of 3-polyfluoroalkyl-3-oxopropanoates and methyl ketones with ammonium acetate affords 6-organyl-4-(polyfluoroalkyl)pyridin-2(1H)-ones (organyl is alkyl, aryl, or hetaryl). The synthesized pyridones were evaluated for antifungal, antibacterial, and analgesic activity.
ABSTRACT
We have developed the convenient methods for synthesis of polyfluorosalicylic acids and their derivatives. For the first time the biological properties of polyfluorosalicylates were investigated in vitro (permeability through the biological membranes, COX-1 inhibitory action) and in vivo (anti-inflammatory, analgesic activities, acute toxicity). Molecular docking of polyfluorinated salicylates confirmed in vitro and in vivo experiments.
Subject(s)
Analgesics/therapeutic use , Anti-Inflammatory Agents, Non-Steroidal/therapeutic use , Cyclooxygenase Inhibitors/therapeutic use , Edema/drug therapy , Salicylates/therapeutic use , Analgesics/chemistry , Analgesics/pharmacokinetics , Analgesics/pharmacology , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Anti-Inflammatory Agents, Non-Steroidal/pharmacokinetics , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cyclooxygenase 1/metabolism , Cyclooxygenase Inhibitors/chemistry , Cyclooxygenase Inhibitors/pharmacokinetics , Cyclooxygenase Inhibitors/pharmacology , Female , Halogenation , Male , Molecular Docking Simulation , Rats, Sprague-Dawley , Rats, Wistar , Salicylates/chemistry , Salicylates/pharmacokinetics , Salicylates/pharmacology , SheepABSTRACT
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 IC50 values, which agrees well with the results of molecular docking.
