Novel Imidazole Aldoximes with Broad-Spectrum Antimicrobial Potency against Multidrug Resistant Gram-Negative Bacteria

Abstract

In the search for a new class of potential antimicrobial agents, five novel N-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 (N-but-3-enyl- and meta- (10) or para- N-chlorobenzyl (11) 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 Enterobacteriaceae isolates carried a multiple extended-spectrum β-lactamases (ESBLs) in comparison to eight clinically relevant antibiotics. N-but-3-enyl-N-meta-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 Escherichia coli and Enterobacter cloacae 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 10 (3 μg:2 μg) showed a strong activity and lower the necessary amount (up to 40-fold) of 10 against five of ESBL-producing isolates (MIC ≤ 1 µg/mL).

Titania‐silica nanoparticles ensemblies assisted heterogeneous catalytic strategy for the synthesis of pharmacologically significant 2,3‐diaryl‐3,4‐dihydroimidazo[4,5‐b]indole scaffolds

“…[18] For instance, Kalhor et al reported a convenient method for the synthesis of imidazole derivatives by involving benzil, aldehyde, and ammonium acetate promoted by Fe 3 O 4 -loaded sulfonated zeolite. [19] Moreover, several catalytic techniques such as the use of InCl 3 .3H 2 O, [20] nanocrystalline-sulphated zirconia, [21] DABCO (1,4-diazabicyclo[2.2.2]octane), [22] nano-TiCl 4 . SiO 2 , [23] nano-SnCl 4 .SiO 2 , [24] HClO 4 -SiO 2, [25] PEG-400, [26] SiO 2 -Pr-SO 3 H, [27] and Ce(SO 4 ) 2 .4H 2 O [28] have been devised for the efficient synthesis of these moieties.…”

“…Their several synthetic analogues possess numerous biological properties, i.e. , anti‐inflamatory, antimicrobial, anticancer, antitubercular, anti‐dengue, anti‐analgesic, anthelmintic, antimycotic, antitumor, and antibacterial activities . Also, the imidazole nucleus has displayed a noteworthy role in some advanced areas of technology such as biological imaging, glucagon receptors, fluorescence labelling agents, modulators of p ‐glycoprotein (P‐gp)‐mediated multidrug resistance (MDR), and chromophores for nonlinear optic systems (NLOS)…”

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“…It is found that pyrazole and imidazole have the wide spectrum of antimicrobial evaluation owing to because the existence of nitrogen atom in fivemembered rings which acts by inhibiting cell wall synthesis or DNA (Deoxyribose nucleic acid) damage [59][60][61] . The antimicrobial activity of these heterocyclics attracted various scientists to attach pyrazole and imidazole rings with the indole nucleus to prevent the problem of microbial resistance.…”

Evaluation of Antimicrobial Potential of the Marine Cyanobacterium, Rivularia mesenterica

“…Preliminary antimicrobial screening of the water extract and extracts obtained with different organic solvents was performed using the disc diffusion assay according to CLSI procedure as previously described [21]. Briefly, 100 µl of suspension containing 10 6 colony-forming units (cfu/ml) of bacterial cells was spread on a Mueller Hinton agar (Becton Dickinson, Sparks, MD, USA).…”