Demirhan Ilter, Necip Adem, Oner Erkan, Gumuscu Nalin, Demirci Ozlem, Gok Yetkin, Doni Nebiye Yentur, Işık Mesut, Rudrapal Mithun, Khan Johra, Ibrahim Randa Mohammad
Department of Electronic-Otomation, Biomedical Device Technology Program, Vocational School of Health Services, Harran University, Sanlıurfa, Türkiye.
Department of Pharmacy Services, Vocational School of Health Services, Harran University, Sanlıurfa, Türkiye.
Front Cell Infect Microbiol. 2025 Jul 18;15:1579916. doi: 10.3389/fcimb.2025.1579916. eCollection 2025.
The discovery of alternative drugs has gained importance due to the many side effects of these drugs used for treatment.
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--imidazol-1-yl)acetophenone and 4-(1--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 H, C 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.
The inhibitory effect against AChE of the series compounds was evaluated as and in silico studies. The results indicated that the compounds showed remarkably potent inhibitory effects on AChE with values ranging from 0.63 ± 0.04 μM to 11.23 ± 1.05 μM and IC 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.
The results suggested that the synthesized compounds showed the potential to be antimicrobial and acetylcholinesterase inhibitors.
由于用于治疗的这些药物存在诸多副作用，发现替代药物变得愈发重要。
本文报道了一系列含有4-乙酰基苯基/4-甲酰基苯基以及吗啉、哌啶、吡咯或吡啶等生物活性杂环基团的不对称咪唑鎓盐的合成。以4-(1-咪唑-1-基)苯乙酮和4-(1-咪唑-1-基)苯甲醛作为盐前体。使用了含有杂环基团的卤代烃，如2-吗啉基乙基盐酸盐、2-吡咯烷基乙基盐酸盐、2-哌啶基乙基盐酸盐和2-吡啶基甲基溴化氢溴化物。因此，通过季铵化方法合成的这些盐的结构中有两个带正电荷的氮。所有盐的结构均通过氢谱、碳谱、傅里叶变换红外光谱和元素分析方法进行了全面表征。设计、合成了一系列咪唑鎓盐（1a-d和2a-d）并通过光谱方法进行了全面表征。
通过实验和计算机模拟研究评估了该系列化合物对乙酰胆碱酯酶的抑制作用。结果表明，这些化合物对乙酰胆碱酯酶显示出显著的强效抑制作用，其抑制常数（Ki）值范围为0.63±0.04μM至11.23±1.05μM，半数抑制浓度（IC50）值范围为0.82±0.06μM至14.75±0.82μM。通过抑制细菌生长测定合成化合物的抗菌活性，以最低抑菌浓度（MIC）值表示。观察到合成化合物表现出抗菌活性，尤其是对革兰氏阴性菌。此外，对细菌的分子对接研究结果支持了我们的抗菌研究结果。
结果表明，合成的化合物具有作为抗菌剂和乙酰胆碱酯酶抑制剂的潜力。
