Syntheses, Protonation Constants and Antimicrobial Activity of 2-Substituted <i>N</i>-alkylimidazole Derivatives

Abstract

A series of N-alkylimidazole-2-carboxylic acid, N-alkylimidazole-2-carboxaldehyde and N-alkylimidazole-2-methanol derivatives [alkyl = benzyl, methyl, ethyl, propyl, butyl, heptyl, octyl and decyl] have been synthesized and the protonation constants determined. The antimicrobial properties of the compounds were tested against Gram-negative (Escherichi coli), Gram-positive (Staphylococcus aureus & Bacillus subtilis subsp. spizizenii) bacterial strains and yeast (C. albicans). Both the disk diffusion and broth microdilution methods for testing the antimicrobial activity showed that N-alkylation of imidazole with longer alkyl chains and the substitution with low pK_a group at 2-position resulted in enhanced antimicrobial activity. Particularly, the N-alkylimidazole-2-carboxylic acids exhibited the best antimicrobial activity due to the low pK_a of the carboxylic acid moiety. Generally, all the N-alkylimidazole derivatives were most active against the Gram-positive bacteria [S. aureus (MIC = 5–160 μg mL^–1) and B. subtilis subsp. spizizenii (5–20 μg mL^–1)], with the latter more susceptible. All the compounds showed poor antimicrobial activity against both Gram-negative (E. coli, MIC = 0.15 to >2500 μg mL^–1) bacteria and all the compounds were inactive against the yeast (Candida albicans).

Keywords: N-alkylimidazoles, antimicrobial, pK_a effect

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