Department of Chemistry, Gava Zang, Zanjan, Iran.
J Enzyme Inhib Med Chem. 2013 Jun;28(3):576-82. doi: 10.3109/14756366.2012.663362. Epub 2012 Mar 7.
A novel method has been developed for the synthesis of α-oxycarbanilino phosphonates through a reaction of α-hydroxyphosphonates with isocyanate under microwave irradiation. The synthesized compounds were evaluated for their acetylcholinesterase (AChE) inhibition potency through IC(50) determination. Molecular modelling studies suggest that the most potent inhibitor (compound 4h, IC(50) = 6.36 µM) is bound to the peripheral site of AChE, which suggests that it decreases the catalytic activity not through binding to the active site but through blocking the entrance of the active site gorge. This puts forward the potential of compound 4h and its derivatives to be used in the design of dual inhibitors: inhibition of the catalytic activity of AChE and of amyloid β aggregation.
一种新方法已经被开发出来，用于通过α-羟基亚膦酸盐与异氰酸酯在微波辐射下的反应来合成α-氧代碳酰苯胺基膦酸酯。通过 IC50 测定评估合成化合物对乙酰胆碱酯酶（AChE）的抑制活性。分子模拟研究表明，最有效的抑制剂（化合物 4h，IC50=6.36μM）与 AChE 的外周结合部位结合，这表明它降低催化活性不是通过与活性部位结合，而是通过阻断活性部位峡谷的入口。这提出了化合物 4h 及其衍生物用于设计双重抑制剂的潜力：抑制 AChE 的催化活性和淀粉样β聚合。
