新型螺环吲哚-苯并噻吩类分子的合成及其作为乙酰胆碱酯酶抑制剂的研究。
Synthesis of a New Class of Spirooxindole-Benzo[]Thiophene-Based Molecules as Acetylcholinesterase Inhibitors.
机构信息
Department of Chemistry, College of Science, King Saud University, P.O. Box 2455, Riyadh 11451, Saudi Arabia.
Department of Chemistry, Faculty of Science, Alexandria University, P.O. Box 426, Ibrahimia, Alexandria 21321, Egypt.
出版信息
Molecules. 2020 Oct 13;25(20):4671. doi: 10.3390/molecules25204671.
A series of new oxindole-based spiro-heterocycles bearing the benzo[]thiophene motif were synthesized via a 1,3-dipolar cycloaddition reaction and their acetylcholinesterase (AChE) inhibitory activity was evaluated. All the synthesized compounds exhibited moderate inhibitory activities against AChE, while was found to be the most active analog with an IC value of 20,840 µM·L. Its molecular structure was a 5-chloro-substituted oxindole bearing benzo[]thiophene and octahydroindole moieties. Based on molecular docking studies, was strongly bound to the catalytic and peripheral anionic sites of the protein through hydrophilic, hydrophobic, and π-stacking interactions with Asp74, Trp86, Tyr124, Ser125, Glu202, Ser203, Trp236, Trp286, Phe297, Tyr337, and Tyr341. These interactions also indicated that the multiplicity of the aromatic core significantly favored its activity.
一系列新型含苯并噻吩结构的吲哚螺杂环化合物通过 1,3-偶极环加成反应合成，并评价了它们对乙酰胆碱酯酶（AChE）的抑制活性。所有合成的化合物对 AChE 均表现出中等抑制活性，而 则表现出最活跃的类似物，IC 值为 20.840 µM·L。其分子结构为 5-氯取代的吲哚，带有苯并噻吩和八氢吲哚部分。基于分子对接研究， 通过与 Asp74、Trp86、Tyr124、Ser125、Glu202、Ser203、Trp236、Trp286、Phe297、Tyr337 和 Tyr341 的亲水、疏水和 π 堆积相互作用， 强烈结合到蛋白质的催化和外周阴离子部位。这些相互作用也表明， 芳核的多重性显著有利于其活性。
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