Table 1_Imidazolium salts carrying two positive charges: design, synthesis, characterization, molecular docking, antibacterial and enzyme inhibitory activities.docx

IntroductionThe discovery of alternative drugs has gained importance due to the many side effects of these drugs used for treatment.
MethodsHerein, 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.
ResultsThe 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 KI 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.
ConclusionsThe results suggested that the synthesized compounds showed the potential to be antimicrobial and acetylcholinesterase inhibitors.

引言：鉴于临床治疗用药物普遍存在多种不良反应，开发替代治疗药物（alternative drugs）的研究价值与日俱增。
方法：本文报道了一系列含4-乙酰苯基/4-甲酰苯基与吗啉、哌啶、吡咯或吡啶等生物活性杂环基团的不对称咪唑鎓盐（unsymmetrical imidazolium salts）的合成工作。以4-(1-H-咪唑-1-基)苯乙酮和4-(1-H-咪唑-1-基)苯甲醛作为盐前体，选用2-吗啉代乙基盐酸盐、2-吡咯烷基乙基盐酸盐、2-哌啶基乙基盐酸盐以及溴化吡啶-2-基甲基氢溴酸盐等含杂环基团的卤代烷作为烷基化试剂。通过季铵化法（quaternization method）合成的此类咪唑鎓盐结构中含有两个带正电荷的氮原子。所有目标盐类的结构均通过1H核磁共振波谱（1H NMR）、13C核磁共振波谱（13C NMR）、傅里叶变换红外光谱（FTIR）以及元素分析（elemental analysis）进行了全面表征。本研究设计、合成了咪唑鎓盐系列化合物1a-d与2a-d，并通过光谱学手段完成了完整表征。
结果：通过体外实验与计算机模拟（in silico）研究，评估了该系列化合物对乙酰胆碱酯酶（AChE）的抑制活性。结果显示，此类化合物对乙酰胆碱酯酶展现出显著的抑制效果，其抑制常数（KI）值范围为0.63 ± 0.04 μM至11.23 ± 1.05 μM，半最大抑制浓度（IC50）值范围为0.82 ± 0.06 μM至14.75 ± 0.82 μM。通过测定最小抑菌浓度（MIC）表征细菌生长抑制率，评估了合成化合物的抗菌活性。研究发现，合成化合物尤其对革兰氏阴性（Gram negative）细菌具有突出的抗菌活性。此外，细菌分子对接（molecular docking）研究结果进一步验证了上述抗菌活性结论。
结论：研究结果表明，所合成的咪唑鎓盐类化合物兼具抗菌活性与乙酰胆碱酯酶抑制潜力，具备开发为相关治疗制剂的潜在价值。