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- Title
Novel Imidazole Aldoximes with Broad-Spectrum Antimicrobial Potency against Multidrug Resistant Gram-Negative Bacteria.
- Authors
Skočibušić, Mirjana; Odžak, Renata; Ramić, Alma; Smolić, Tomislav; Hrenar, Tomica; Primožič, Ines
- Abstract
In the search for a new class of potential antimicrobial agents, five novel <italic>N</italic>-substituted imidazole 2-aldoximes and their six quaternary salts were evaluated. The antimicrobial activity was assessed against a panel of representative Gram-positive and Gram-negative bacteria, including multidrug resistant bacteria. All compounds demonstrated potent in vitro activity against the tested microorganisms, with MIC values ranging from 6.25 to 50.0 μg/mL. Among the tested compounds, two quaternary compounds (<italic>N</italic>-but-3-enyl- and <italic>meta</italic>- (<bold>10</bold>) or <italic>para</italic>- <italic>N</italic>-chlorobenzyl (<bold>11</bold>) imidazolium 2-aldoximes) displayed the most potent and broad-spectrum activity against both Gram-positive and Gram-negative bacterial strains. The broth microdilution assay was also used to investigate the antiresistance efficacy of the both most active compounds against a set of <italic>Enterobacteriaceae</italic> isolates carried a multiple extended-spectrum β-lactamases (ESBLs) in comparison to eight clinically relevant antibiotics. <italic>N</italic>-but-3-enyl-<italic>N-meta</italic>-chlorobenzyl imidazolium 2-aldoxime was found to possess promising antiresistance efficacy against a wide range of β-lactamases producing strains (MIC 2.0 to 16.0 μg/mL). Best results for that compound were obtained against <italic>Escherichia coli</italic> and <italic>Enterobacter cloacae</italic> producing multiple β-lactamases form A and C molecular classes, which were 32- and 128-fold more potent than ceftazidime and cefotaxime, respectively. To visualize the results, principal component analysis was used as an additional classification tool. The mixture of ceftazidime and compound <bold>10</bold> (3 μg:2 μg) showed a strong activity and lower the necessary amount (up to 40-fold) of <bold>10</bold> against five of ESBL-producing isolates (MIC ≤ 1 µg/mL).
- Subjects
IMIDAZOLES; ANTI-infective agents; BIOCIDES; ALDOXIMES; MICROORGANISMS
- Publication
Molecules, 2018, Vol 23, Issue 5, p1212
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules23051212