A number of novel naphthalimido and phthalimido vanillin derivatives were synthesised, and evaluated as antioxidants and cholinesterase inhibitors in vitro. Antioxidant activity was assessed using DPPH, FRAP, and ORAC assays. All compounds demonstrated enhanced activity compared to the parent compound, vanillin. They also exhibited BuChE selectivity in Ellman’s assay. A lead compound, 2a (2-(3-(bis(4-hydroxy-3-methoxybenzyl)amino)propyl)-1H-benzo[de]isoquinoline-1,3(2H)-dione), was identified and displayed strong antioxidant activity (IC₅₀ of 16.67 µM in the DPPH assay, a 25-fold increase in activity compared to vanillin in the FRAP assay, and 9.43 TE in the ORAC assay). Furthermore, 2a exhibited potent BuChE selectivity, with an IC₅₀ of 0.27 µM which was around 53-fold greater than the corresponding AChE inhibitory activity. Molecular modelling studies showed that molecules with bulkier groups, as in 2a, exhibited better BuChE selectivity. This work provides a promising basis for the development of multi-target hybrid compounds based on vanillin as potential AD therapeutics.

合成了许多新颖的萘二甲酰亚胺和邻苯二甲酰亚胺香兰素衍生物，并在体外评价为抗氧化剂和胆碱酯酶抑制剂。使用DPPH，FRAP和ORAC分析评估抗氧化活性。与母体化合物香草醛相比，所有化合物均显示出增强的活性。他们还在Ellman分析中显示BuChE选择性。鉴定出一种铅化合物2a（2-（3-（双（4-（3-羟基-3-甲氧基苄基）氨基）丙基）-1H-苯并[de]异喹啉-1,3（2H）-二酮）并显示出较强的抗氧化剂活性（在DPPH分析中，IC ₅₀为16.67 µM，与FRAP分析中的香兰素相比，活性提高了25倍，在ORAC分析中与9.43 TE相比）。此外，具有IC的2a表现出有效的BuChE选择性0.27 µM中的₅₀，比相应的AChE抑制活性高约53倍。分子建模研究表明，具有较大基团的分子（如2a中所示）表现出更好的BuChE选择性。这项工作为开发基于香草醛作为潜在的AD治疗剂的多目标杂化化合物提供了有希望的基础。