School of Pharmaceutical Sciences, Universiti Sains Malaysia, Minden 11800, Penang, Malaysia.
Eur J Med Chem. 2013 Sep;67:221-9. doi: 10.1016/j.ejmech.2013.06.054. Epub 2013 Jul 4.
Series of hitherto unreported piperidone grafted pyridopyrimidines synthesized through ionic liquid mediated multi-component reaction. These compounds were evaluated for their inhibitory activities against AChE and BChE enzymes. All the compounds displayed considerable potency against AChE with IC50 values ranging from 0.92 to 9.11 μM, therein compounds 6a, 6h and 6i displayed superior enzyme inhibitory activities compared to standard drug with IC50 values of 0.92, 1.29 and 2.07 μM. Remarkably, all the compounds displayed higher BChE inhibitory activity compared to galantamine with IC50 values of 1.89-8.13 μM. Molecular modeling, performed for the most active compounds using three dimensional crystal structures of TcAChE and hBChE, disclosed binding template of these inhibitors into the active site of their respective enzymes.
通过离子液体介导的多组分反应合成了一系列迄今未报道的哌啶酮接枝吡啶并嘧啶。评估了这些化合物对 AChE 和 BChE 酶的抑制活性。所有化合物对 AChE 均显示出相当大的抑制活性，IC50 值范围为 0.92-9.11 μM，其中化合物 6a、6h 和 6i 的酶抑制活性优于标准药物，IC50 值分别为 0.92、1.29 和 2.07 μM。值得注意的是，所有化合物对 BChE 的抑制活性均高于加兰他敏，IC50 值为 1.89-8.13 μM。使用 TcAChE 和 hBChE 的三维晶体结构对最活跃的化合物进行分子建模，揭示了这些抑制剂进入其各自酶的活性部位的结合模板。
