RESEARCH ARTICLE

 

Syntheses, protonation constants and antimicrobial activity of 2-substituted N-alkylimidazole derivatives

 

 

Phumelele Kleyi^I; Ryan S. Walmsley^I; Isaac Z. Gundhla^I; Tara A. Walmsley^II; Tembisa I. Jauka^I; Joanna Dames^II; Roderick B. Walker^III; Nelson Torto^I; Zenixole R. Tshentu^{I, *}

^IDepartment of Chemistry, Rhodes University, P.O. Box 94, Grahamstown, 6140, South Africa
^IIDepartment of Biochemistry, Microbiology and Biotechnology, Rhodes University, P.O. Box 94, Grahamstown, 6140, South Africa
^IIIDivision of Pharmaceutics, Faculty of Pharmacy, Rhodes University, P.O. Box 94, Grahamstown, 6140, South Africa

 

 

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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 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, pK_a effect

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Acknowledgements

We thank the SA National Research Foundation, Medical Research Council (MRC) and Water Research Commission (WRC) for funding.

 

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Received 31 May 2012
Revised 16 July
Accepted 3 October 2012

 

 

* To whom correspondence should be addressed. E-mail: z.tshentu@ru.ac.za