Imidazole and Imidazolium Antibacterial Drugs Derived from Amino Acids

Abstract

The antibacterial activity of imidazole and imidazolium salts is highly dependent upon their lipophilicity, which can be tuned through the introduction of different hydrophobic substituents on the nitrogen atoms of the imidazole or imidazolium ring of the molecule. Taking this into consideration, we have synthesized and characterized a series of imidazole and imidazolium salts derived from L-valine and L-phenylalanine containing different hydrophobic groups and tested their antibacterial activity against two model bacterial strains, Gram-negative E. coli and Gram-positive B. subtilis. Importantly, the results demonstrate that the minimum bactericidal concentration (MBC) of these derivatives can be tuned to fall close to the cytotoxicity values in eukaryotic cell lines. The MBC value of one of these compounds toward B. subtilis was found to be lower than the IC50 cytotoxicity value for the control cell line, HEK-293. Furthermore, the aggregation behavior of these compounds has been studied in pure water, in cell culture media, and in mixtures thereof, in order to determine if the compounds formed self-assembled aggregates at their bioactive concentrations with the aim of determining whether the monomeric species were in fact responsible for the observed antibacterial activity. Overall, these results indicate that imidazole and imidazolium compounds derived from L-valine and L-phenylalanine—with different alkyl lengths in the amide substitution—can serve as potent antibacterial agents with low cytotoxicity to human cell lines.

Hypochlorite-Activated Fluorescence Emission and Antibacterial Activities of Imidazole Derivatives for Biological Applications

“…In sharp contrast, almost all imidazolium salts ( R 1 IR 2 ) exhibited a stronger antibacterial effect, including against ESBL-EC and MRSA ( p > 2.4). The antibacterial efficiency of R 1 IR 2 is quite similar to that of dehydroepiandrosterone-derived ( Hryniewicka et al, 2021 ), peptide-conjugated ( Reinhardt et al, 2014 ), ethoxyether-functionalized ( Huang et al, 2011 ), amino acid–derived ( Valls et al, 2020 ), polydiacetylene-conjugated ( Lee et al, 2016 ), and unsymmetrically substituted ( Çoban et al, 2017 ; Duman et al, 2019 ) imidazolium salts in previous reports. Furthermore, the antibacterial activity of imidazolium salts ( R 1 IR 2 ) increased following the substitution of methyl and bromobenzyl with dibromobenzyl groups and the change from one to two dibromobenzyl groups ( Table 3 ).…”

Antimicrobial Ionic Liquid‐Based Materials for Biomedical Applications

“…compounds. [77] Although bis-cations have been reported to be more effective than the related mono-cation, other factors may affect and improve the antibacterial potency of the mono-cations.…”

Synthesis, characterization, In-Silico studies, and anti-inflammatory activity of Novel Imidazole-5(4H)-Ones

“…Out of these heterocyclic compounds, imidazole and its derivatives have a wide variety of biological activities. [3][4][5][6][7][8] Imidazole is an important group of heterocyclic compounds that are biologically active and of significant importance in medicinal chemistry. The imidazole ring is an important pharmacophore in modern drug discovery.…”