Abstract
The antimicrobial activity of sixteen new N-heteroarylated 1H-(benz)imidazoles was evaluated against clinically relevant bacteria (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and fungi (Candida, Aspergillus and dermatophyte) species according to the Clinical and Laboratory Standards Institute guidelines. None of the tested compounds were active against Gram negative bacteria, but only against S. aureus, that was particularly susceptible to N-thianthrenyl- and N-dibenzothienyl imidazole derivatives. Most of the imidazole derivatives showed a broad spectrum of antifungal activity in all tested fungal strains, including fluconazole-resistant species, with a particularly low minimum inhibitory concentration (MIC) for dermatophytes. N-(dibenzofuran-4-yl)-1H-imidazole (1) and N-(dibenzothien-4-yl)-1H-imidazole (3) showed the highest antifungal potential, being most active against Candida albicans. Some N-heteroarylated benzimidazoles showed low activity for fungi with the exception of 3-(1H-benzo [d]imidazol-1-yl)quinoline (14) which was selective against dermatophytes (MIC=4-16 µg/mL). The effect of the active compounds in the inhibition of the dimorphic transition, ergosterol biosynthesis and mitochondrial activity was evaluated in C. albicans. Compounds 1 and 3 showed the capacity to inhibit the germ tube formation in C. albicans, reduced the ergosterol production and impaired the mitochondrial function. Compounds 1 and 3 showed antimicrobial activity and low cytotoxicity, being of interest for further investigation concerning specially the development of new antifungal agents.
Keywords: N-heteroarylated 1H-(benz)imidazoles, antibacterial activity, antifungal activity, ergosterol biosynthesis, germ tubes, mitochondrial activity, structure-activity relationship.
Mini-Reviews in Medicinal Chemistry
Title:Antimicrobial Activity and Mechanism of Action of New N-heteroaryl-1H- (benz)Imidazoles
Volume: 14 Issue: 11
Author(s): Eugenia Pinto, Helena Neves, Karnjana Hrimpeng, Ana-Filipa Silva, Agathe Begouin, Graciliana Lopes and Maria-Joao R.P. Queiroz
Affiliation:
Keywords: N-heteroarylated 1H-(benz)imidazoles, antibacterial activity, antifungal activity, ergosterol biosynthesis, germ tubes, mitochondrial activity, structure-activity relationship.
Abstract: The antimicrobial activity of sixteen new N-heteroarylated 1H-(benz)imidazoles was evaluated against clinically relevant bacteria (Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa) and fungi (Candida, Aspergillus and dermatophyte) species according to the Clinical and Laboratory Standards Institute guidelines. None of the tested compounds were active against Gram negative bacteria, but only against S. aureus, that was particularly susceptible to N-thianthrenyl- and N-dibenzothienyl imidazole derivatives. Most of the imidazole derivatives showed a broad spectrum of antifungal activity in all tested fungal strains, including fluconazole-resistant species, with a particularly low minimum inhibitory concentration (MIC) for dermatophytes. N-(dibenzofuran-4-yl)-1H-imidazole (1) and N-(dibenzothien-4-yl)-1H-imidazole (3) showed the highest antifungal potential, being most active against Candida albicans. Some N-heteroarylated benzimidazoles showed low activity for fungi with the exception of 3-(1H-benzo [d]imidazol-1-yl)quinoline (14) which was selective against dermatophytes (MIC=4-16 µg/mL). The effect of the active compounds in the inhibition of the dimorphic transition, ergosterol biosynthesis and mitochondrial activity was evaluated in C. albicans. Compounds 1 and 3 showed the capacity to inhibit the germ tube formation in C. albicans, reduced the ergosterol production and impaired the mitochondrial function. Compounds 1 and 3 showed antimicrobial activity and low cytotoxicity, being of interest for further investigation concerning specially the development of new antifungal agents.
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Pinto Eugenia, Neves Helena, Hrimpeng Karnjana, Silva Ana-Filipa, Begouin Agathe, Lopes Graciliana and Queiroz R.P. Maria-Joao, Antimicrobial Activity and Mechanism of Action of New N-heteroaryl-1H- (benz)Imidazoles, Mini-Reviews in Medicinal Chemistry 2014; 14 (11) . https://dx.doi.org/10.2174/1389557514666141029225524
DOI https://dx.doi.org/10.2174/1389557514666141029225524 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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