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South African Journal of Chemistry

versión On-line ISSN 1996-840X
versión impresa ISSN 0379-4350

S.Afr.j.chem. (Online) vol.65  Durban  2012

 

RESEARCH ARTICLE

 

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

 

 

Phumelele KleyiI; Ryan S. WalmsleyI; Isaac Z. GundhlaI; Tara A. WalmsleyII; Tembisa I. JaukaI; Joanna DamesII; Roderick B. WalkerIII; Nelson TortoI; Zenixole R. TshentuI, *

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

 

 


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 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


 

 

Full text available only in PDF format.

 

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

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