Synthesis and antimicrobial activity of a series of optically active quaternary ammonium salts derived from phenylalanine

Miloš Lukáč 1 , Ivan Lacko 1 , Marián Bukovský 2 , Zuzana Kyselová 1 , Janka Karlovská 3 , Branislav Horváth 4 , and Ferdinand Devínsky 1
  • 1 Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Bratislava, 832 32, Slovakia
  • 2 Department of Cellular and Molecular Biology of Drugs, Faculty of Pharmacy, Comenius University, Bratislava, 832 32, Slovakia
  • 3 Department of Physical Chemistry of Drugs, Faculty of Pharmacy, Comenius University, Bratislava, 832 32, Slovakia
  • 4 Institute of Chemistry, Faculty of Natural Science, Comenius University, Bratislava, 842 15, Slovakia

Abstract

We synthesized nine quaternary ammonium compounds (QUATs) starting from phenylalanine, N-alkyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromides, which were prepared as optically pure substances. Five compounds were prepared as S-enantiomers and four compounds as R-enantiomers. These compounds were evaluated by their activities against bacteria and fungi. Three microbial strains were used in the study: the gram-negative bacteria Escherichia coli, the gram-positive bacteria Staphylococcus aureus and the fungi Candida albicans. The activities were expressed as minimum bactericidal or fungicidal concentrations (MBC). The most active compounds were (2S)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide and (2R)-N-tetradecyl-N,N-dimethyl-(1-hydroxy-3-phenylpropyl)-2-ammonium bromide, with MBC values exceeding those of commercial benzalkoniumbromide (BAB) used as standard. The relationships between structure and biological activity of the tested QUATs were quantified by the bilinear model (QSAR) and are discussed.

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