South African Journal of Chemistry
On-line version ISSN 1996-840X
KLEYI, Phumelele et al. Syntheses, protonation constants and antimicrobial activity of 2-substituted N-alkylimidazole derivatives. S.Afr.j.chem. (Online) [online]. 2012, vol.65, pp. 231-238. ISSN 1996-840X.
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 pKa 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 pKa of the carboxylic acid moiety. Generally, all the N-alkylimidazole derivatives were most active against the Gram-positive bacteria [S. aureus (MIC = 5-160 mL-1) and B. subtilis subsp. spizizenii (5-20 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 mL-1) bacteria and all the compounds were inactive against the yeast (Candida albicans).
Keywords : N-alkylimidazoles; antimicrobial; pKa effect.