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. 2025 Jul 18:15:1579916.
doi: 10.3389/fcimb.2025.1579916. eCollection 2025.

Imidazolium salts carrying two positive charges: design, synthesis, characterization, molecular docking, antibacterial and enzyme inhibitory activities

Ilter Demirhan  1 , Adem Necip  2 , Erkan Oner  3 , Nalin Gumuscu  4   5 , Ozlem Demirci  6 , Yetkin Gok  6 , Nebiye Yentur Doni  7 , Mesut Işık  8 , Mithun Rudrapal  9 , Johra Khan  10   11 , Randa Mohammad Ibrahim  10   12
Affiliations

Imidazolium salts carrying two positive charges: design, synthesis, characterization, molecular docking, antibacterial and enzyme inhibitory activities

Ilter Demirhan et al. Front Cell Infect Microbiol. .

Abstract

Introduction: The discovery of alternative drugs has gained importance due to the many side effects of these drugs used for treatment.

Methods: Herein, the synthesis of a series of unsymmetrical imidazolium salts containing 4-acetylphenyl/4-formylphenyl and bioactive heterocyclic groups such as morpholine, piperidine, pyrrole or pyridine was reported. 4-(1-H-imidazol-1-yl)acetophenone and 4-(1-H-imidazol-1-yl)benzaldehyde were used as salt precursors. Alkyl halides containing heterocyclic groups such as 2-morpholinoethyl hydrochloride, 2-pyrrolidinoethyl hydrochloride, 2-piperidinoethyl hydrochloride and pyridin-2-ylmethyl bromide hydrobromide were used. Thus, there are two positively charged nitrogens in the structure of these salts synthesized by the quaternization method. The structures of all salts were fully characterized by 1H, 13C NMR, FTIR spectroscopic and elemental analysis methods. the a series of imidazolium salts (1a-d and 2a-d) were designed, synthesized and fully characterized by spectroscopic methods.

Results: The inhibitory effect against AChE of the series compounds was evaluated as in vitro and in silico studies. The results indicated that the compounds showed remarkably potent inhibitory effects on AChE with K I values ranging from 0.63 ± 0.04 μM to 11.23 ± 1.05 μM and IC50 values spanning from 0.82 ± 0.06 μM to 14.75 ± 0.82 μM. The antimicrobial activities of the synthesized compounds were measured by inhibition of bacterial growth expressed as minimum inhibitory concentration (MIC) values. It was observed that the synthesized compounds exhibited antimicrobial activity especially against Gram negative bacteria. In addition, the results of molecular docking studies of bacteria supported our antimicrobial results.

Conclusions: The results suggested that the synthesized compounds showed the potential to be antimicrobial and acetylcholinesterase inhibitors.

Keywords: N-heterocyclic carbene; acetylcholinesterase; anti-Alzheimer; antimicrobial; imidazolium salt.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Structural features of imidazolium salts carrying two positive charges.
Figure 2
Figure 2
Synthesis of imidazolium salts containing 4-acetylphenyl.
Figure 3
Figure 3
Synthesis of imidazolium salts containing 4-formylphenyl.
Figure 4
Figure 4
Synthesis mechanism of imidazolium salts (1a-d and 2a-d).
Figure 5
Figure 5
Chemical binding targets of 1a-2d in S. aureus bacterial structure.
Figure 6
Figure 6
Chemical binding targets of 1a-2d in E. coli bacterial structure.
Figure 7
Figure 7
Chemical binding targets of 1a-2d in E. Faecalis bacterial structure.
Figure 8
Figure 8
Chemical binding targets of 1a-2d in P. aeruginosa bacterial structure.
Figure 9
Figure 9
Binding model of 1a-2d in the bacterial structure of S. aureus.
Figure 10
Figure 10
Binding model of 1a-2d in the bacterial structure of E. Coli.
Figure 11
Figure 11
Binding model of 1a-2d in the bacterial structure of E. Faecalis.
Figure 12
Figure 12
Binding model of 1a-2d in the bacterial structure of P. aeruginosa.
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