Synthesis of quaternary ammonium saltsisonicotinic and nicotinic hydrazones acids and their anti-inflammatory activity

Abstract

Currently, the number of infections caused by strains of bacteria that are not sensitive to antibiotics and antiseptics is growing worldwide. A similar increase in bacterial resistance is observed for both nosocomial infections and community-acquired human-to-human infections. An important task for chemists and pharmacologists is the synthesis of new compounds and the establishment of a structure-bioactivity relationship. The purpose of this work is to study the effect of the structure of quaternary ammonium derivatives of hydrazones of isonicotinic and nicotinic acids on the manifestation of their anti-inflammatory properties. Results and discussion. The alkylation of nicotinic acid hydrazones produced their new quaternary ammonium salts (43.7-70.7%). The methodology for the synthesis of quaternary ammonium compounds of hydrazones included obtaining a variety of structures by introducing one or two fluorine and bromine-containing fragments into their structure. The structure of compounds was confirmed by 1H, 13C NMR spectroscopy. Conclusion. New quaternary ammonium salts of nicotinic acid hydrazones have been obtained. The study of anti-inflammatory activity was carried out using the method of formalin paw edema in rats. The acute inflammatory reaction was reproduced by subplantar administration of 2% formalin solution. Compared with ibuprofen at a dosage of 100 mg/kg, these compounds were ineffective (p2<0.05). According to the results of the analysis of possible pharmacological effects, it was also revealed that new compounds may have an effect on the regulation and production of ketone bodies, the enzymatic activity of transaminases. New alkylated hydrazones of isonicotinic and nicotinic acids may be of interest for studying their antituberculous and antiviral activities.