A new series of 4-oxobenzo[d]1,2,3-triazin-pyridinium-phenylacetamide hybrids 8a–p was designed, synthesized, and screened as the potential cholinesterase inhibitors against acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). Obtained anti-cholinesterase activities demonstrated that all the title compounds exhibited excellent inhibition against BuChE and moderate inhibitory activity toward AChE in comparison to standard cholinesterase inhibitor donepezil. For example, compound 8e exhibited about 49-fold higher inhibitory activity than donepezil (IC 50 = 3.2 ± 0.3 μM) against BuChE. This compound inhibited BuChE via a mixed-type inhibition mode. This finding demonstrated that compound 8e in addition to catalytic anionic site (CAS) can also interact with the peripheral anionic site (PAS) of BuChE. Molecular modeling and molecular dynamic studies were also performed on synthesized compounds.

中文翻译：

---

4-氧代苯并[d]1,2,3-三嗪-吡啶鎓-苯基乙酰胺衍生物作为新型抗阿尔茨海默病药物：设计、合成、体外评价、分子建模和分子动力学研究

设计、合成和筛选了一系列新的 4-氧代苯并[d]1,2,3-三嗪-吡啶-苯基乙酰胺杂化物 8a-p，作为针对乙酰胆碱酯酶 (AChE) 和丁酰胆碱酯酶 (BuChE) 的潜在胆碱酯酶抑制剂。获得的抗胆碱酯酶活性表明，与标准胆碱酯酶抑制剂多奈哌齐相比，所有标题化合物均表现出对 BuChE 的出色抑制和对 AChE 的中等抑制活性。例如，化合物 8e 对 BuChE 的抑制活性比多奈哌齐 (IC 50 = 3.2 ± 0.3 μM) 高约 49 倍。该化合物通过混合型抑制模式抑制 BuChE。这一发现表明，化合物 8e 除了催化阴离子位点 (CAS) 外，还可以与 BuChE 的外围阴离子位点 (PAS) 相互作用。