Antimicrobial activity of amine oxides: mode of action and structure-activity correlation

Abstract

The effect of N-alkyl derivatives of saturated heterocyclic amine oxides on the growth and metabolism of microorganisms has been studied. 4-Dodecylmorpholine-N-oxide inhibited the differentiation and growth of Bacillus cereus, of different species of filamentous fungi, and of the yeast Saccharomyces cerevisiae. For vegetative cells, the effect of 4-dodecylmorpholine-N-oxide was lethal. Cells of S. cerevisiae, after interaction with 4-dodecylmorpholine-N-oxide, released intracellular K(+) and were unable to oxidize or ferment glucose. The functions of isolated yeast mitochondria were also impaired. 4-Dodecylmorpholine-N-oxide at growth-inhibiting concentrations induced rapid lysis of osmotically stabilized yeast protoplasts, with the rate of lysis a function of temperature and of amine oxide concentration. A study of the relationships between structure, antimicrobial activity, and cytolytic activity was made with a group of structurally different amine oxides involving a series of homologous 4-alkylmorpholine-N-oxides, 1-alkylpiperidine-N-oxides, 1-dodecylpyrrolidine-N-oxide, 1-dodecylperhydroasepine-N-oxide, and N,N-dimethyldodecylamine oxide. Disorganization of the membrane structure after interaction of cells with the tested amine oxides was primarily responsible for the antimicrobial activity of the amine oxides. This activity was found to be dependent on the chain length of the hydrophobic alkyl group and was only moderately influenced by other substituents of the polarized N-oxide group.