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Information × Registration Number 0224U033156, (0124U003081) , R & D reports Title Structurally modified natural compounds of the bromotyrosine series as inhibitors of bacterial biofilms for the prevention and treatment of persistent infections popup.stage_title Конструювання, синтез та дослідження антибіоплівкової активності біфункціоналізованих похідних 3,5-дибромо-4-гідроксифенілоцтової кислоти. Синтез нових гетарилзаміщених похідних 3,5-дибромо-4-гідроксифенілоцтової кислоти з антибіоплівковою дією. Head Smolii Oleh B., д.х.н. Registration Date 19-12-2024 Organization V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine popup.description1 The research aims to synthesize structurally modified bromotyrosine derivatives of natural origin in order to develop the promising inhibitors of bacterial biofilms, to study the antimicrobial activity of the obtained compounds against biofilm microorganisms and to clarify certain aspects of the inhibitory mechanism. The project will focus on the development of effective methods for modifying bromotyrosine analogs with various pharmacophore groups and fragments of known drugs, as well as researching antibacterial and antibiofilm activity against gram-positive and gram-negative bacteria. popup.description2  Approaches to obtaining structural analogues of natural compounds of the bromotyrosine series based on bifunctionalized (3,5- dibromo-4-hydroxyphenyl)acetic acid derivatives were found. New quaternary ammonium compounds with long alkyl chains were synthesized and their antibacterial and antibiofilm activity against S. aureus, E. coli and P. aeruginosa was evaluated. Most of the compounds showed strong inhibition of biofilm formation of S. aureus ATCC 25923, P. aeruginosa PA01 and P. aeruginosa CRPA at a concentration of 5.0 μg/ml. The ammonium salt, containing a pyrrolidine ring, a four-carbon linker and a decyl alkyl chain, demonstrated 100% inhibition of most of the bacterial biofilms tested. Based on hetaryl-substituted derivatives of (3,5- dibromo-4-hydroxyphenyl)acetic acid, a simple preparative method for the synthesis of bis-quaternary ammonium salts was developed and in vitro antibacterial and antibiofilm activity against E. coli, S. aureus, P. aeruginosa, including antibiotic-resistant strains, was studied. Bis-quaternary ammonium salts showed antibacterial activity with MIC values in the range from 25.0 to 200.0 μg/ml. It was found that two compounds with an ester group and a propyl linker, and a piperidinyl substituent and a butyl linker reduced biofilm formation against S. aureus ATCC 25923, P. aeruginosa PA01, E. coli ATCC 25922 and antibiotic-resistant P. aeruginosa by 92-97% at a concentration of 100.0 μg/ml. The results obtained indicate the prospects for further research into the development of effective antimicrobial and antibiofilm agents based on synthetic analogues of bromotyrosine alkaloids. Product Description popup.authors Hodyna Diana M. Metelytsia Larysa O. Muzychka Liubov V. popup.nrat_date 2024-12-19 Close