ANTIMICROBIAL ACTIVITY OF NEW DERIVATIVES OF 4- (HET)ARYL-4-OXOBUT-2-ENOIC ACIDS

Introduction. The actual problem of Russian pharmacy is to fight antibiotic resistance. The results of investigations have indicated that 4-(het)aryl-4-oxobut-2-enoic acid derivatives that contain 2-N-substituted fragments exhibit a wide spectrum of biological activity. The authors have previously obtained low-toxic 4-aryl-2-(4-arylamino)-1-[piperazine-1-yl]but-2-ene-1,4-dione hydrochlorides and 4-(het)aryl-2-{2-[2-(3-R-adamantane-1-yl)-2-oxoethylidene]hydrazinyl}-4-oxobut-2-enoates of sodium with a good water solubility, but their antimicrobial activity has not been investigated. Objective: to investigate the antimicrobial activity of N-substituted 2-arylamino- and 2-hydrazinyl-4-(het)aryl-4-oxobut-2-enoic acid derivatives containing pharmacophoric adamantyl and piperazinyl fragments, as well as their water-soluble salts. Material and methods. The antimicrobial activity of the compounds was tested using the test cultures of the microorganisms Staphylococcus aureus ATCC 6538-P and Escherchia coli ATCC 25922. Results. The investigation revealed the regularity of enhancing antimicrobial activity during transition from the starting derivatives of acids to their salts. The highest activity was shown by the substances having an adamantyl fragment and electron-donor groups in the aryl radical. Twelve substances and nine compounds had activities at the level or higher than the effect of chlorhexidine and dioxidine, respectively. Conclusion. The antimicrobial activity of water-soluble compounds having an adamantyl fragment was found to be much higher than that of piperazinyl-containing compounds. Substances with electron-donor substituents in aryl at the C (4) atom of but-2-enoic acid exerted a high activity. A compound, the activity of which against the examined bacterial strains exceeded or was at the level of the comparison preparations, was found.