Antimicrobial Activity and Mechanism of Action of New N-heteroaryl-1H-(benz)Imidazoles

• Type: Another Publication in an International Scientific Journal
• Date: 2014

Authors

Eugenia Pinto (Author) FFUP; Helena Neves (Author) Other; Karnjana Hrimpeng (Author) Other; Ana Filipa Silva (Author) Other; Agathe Begouin (Author) Other; Graciliana Lopes (Author) Other; Maria Joao R P Queiroz (Author) Other

Journal

Title: Mini-Reviews in Medicinal Chemistry

Vol. 14

Pages: 941-952

ISSN: 1389-5575

Publisher: Bentham Science

Indexing

ISI Web of Knowledge - 2 Citations

Scopus - 3 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: P-009-YWZ

Abstract (EN): 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 mu g/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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 12