School of Chemistry, College of Science, University of Tehran, Tehran, Iran.
Cellular and Molecular Biology Research Center, Health Research Institute, Babol University of Medical Sciences, Babol, Iran.
Bioorg Chem. 2019 Jun;87:506-515. doi: 10.1016/j.bioorg.2019.03.012. Epub 2019 Mar 6.
A new series of benzyl pyridinium-2,4-dioxochroman derivatives 7a-o was synthesized and evaluated as new anti-Alzheimer agents. Among the synthesized compounds, the compounds 7f and 7i exhibited the most potent anti-AChE and anti-BuChE activities, respectively. The kinetic study of the compound 7f revealed that this compound inhibited AChE in a mixed-type inhibition mode. Furthermore, the docking study of the compounds 7f and 7i showed that these compounds bound to both the catalytic site (CS) and peripheral anionic site (PAS) of AChE and BuChE, respectively. The compound 7f also exhibited a greater self-induced Aβ peptide aggregation inhibitory activity in compare to donepezil. Furthermore, the neuroprotective activity of this compound at 20 μM was comparable to that of the standard neuroprotective agent (quercetin).
合成了一系列新的苄基吡啶-2,4-二氧代色满衍生物 7a-o，并将其作为新型抗阿尔茨海默病药物进行了评价。在所合成的化合物中，化合物 7f 和 7i 分别表现出最强的抗 AChE 和抗 BuChE 活性。化合物 7f 的动力学研究表明，该化合物以混合抑制模式抑制 AChE。此外，化合物 7f 和 7i 的对接研究表明，这些化合物分别与 AChE 和 BuChE 的催化位点 (CS) 和外周阴离子位点 (PAS) 结合。与多奈哌齐相比，化合物 7f 还表现出更强的自身诱导 Aβ 肽聚集抑制活性。此外，该化合物在 20μM 时的神经保护活性与标准神经保护剂（槲皮素）相当。
