Jelčić Antonija, Talić Stanislava, Odak Ilijana, Pongrac Paula, Štefok Dora, Škorić Irena
Department of Organic Chemistry, University of Zagreb Faculty of Chemical Engineering and Technology, Trg Marka Marulića 19, HR-10 000 Zagreb, Croatia.
Department of Chemistry, Faculty of Science and Education, University of Mostar, Matice Hrvatske bb, 88 000 Mostar, Bosnia and Herzegovina.
Molecules. 2025 Aug 20;30(16):3439. doi: 10.3390/molecules30163439.
It has been shown previously that thienobenzo-1,2,3-triazoles exhibit very good selective inhibition toward butyrylcholinesterase (BChE), while the same derivatives converted into salts also display inhibitory activity against acetylcholinesterase (AChE), enzymes relevant to Alzheimer's disease therapy. They show even better BChE inhibition potential than neutral analogs.
This study presents the synthesis and biological evaluation of a novel series of charged thienobenzo-1,2,3-triazolinium salts (-) as inhibitors of AChE and BChE. The basic skeleton of the targeted compounds was synthesized via a photochemical method and subsequently converted into corresponding bromide salts. Their structures were confirmed using NMR and HRMS analyses.
In vitro testing showed that all synthesized compounds exhibit moderate to strong BChE inhibition and, to a lesser extent, AChE inhibition. Compounds and emerged as the most potent AChE inhibitors (IC ~ 2.6-3.2 µM), while compounds , , and demonstrated excellent and selective BChE inhibition (IC ~ 0.3-0.4 µM), outperforming the reference drug galantamine. Anti-inflammatory evaluation revealed limited activity, with compound slightly reducing LPS-induced TNF-α production at the highest tested concentration.
These findings highlight the role of the electric charge and substituent type in modulating biological activity and confirm the therapeutic potential of these molecules as dual cholinesterase inhibitors for further development in neurodegenerative disease treatment.
先前的研究表明，噻吩并苯并-1,2,3-三唑对丁酰胆碱酯酶（BChE）表现出非常好的选择性抑制作用，而同样的衍生物转化为盐后对乙酰胆碱酯酶（AChE）也具有抑制活性，这两种酶与阿尔茨海默病的治疗相关。它们表现出比中性类似物更好的BChE抑制潜力。
本研究介绍了一系列新型带电荷的噻吩并苯并-1,2,3-三唑鎓盐（-）作为AChE和BChE抑制剂的合成及生物学评价。通过光化学方法合成了目标化合物的基本骨架，随后将其转化为相应的溴化物盐。使用NMR和HRMS分析确认了它们的结构。
体外测试表明，所有合成化合物均表现出中度至强烈的BChE抑制作用，对AChE的抑制作用较小。化合物 和 是最有效的AChE抑制剂（IC2.6 - 3.2 µM），而化合物 、 和 表现出优异的选择性BChE抑制作用（IC0.3 - 0.4 µM），优于参比药物加兰他敏。抗炎评价显示活性有限，化合物 在最高测试浓度下略微降低了LPS诱导的TNF-α产生。
这些发现突出了电荷和取代基类型在调节生物活性中的作用，并证实了这些分子作为双重胆碱酯酶抑制剂在神经退行性疾病治疗中进一步开发的治疗潜力。
