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用于阿尔茨海默病的菲咯啉-四氢喹啉研究中的实验与理论方法

Experimental and Theoretical Approaches in the Study of Phenanthroline-Tetrahydroquinolines for Alzheimer's Disease.

作者信息

Duarte Yorley, Gutierrez Margarita, Álvarez Rocío, Alzate-Morales Jans H, Soto-Delgado Jorge

机构信息

Facultad de Ciencias de la Vida, Center for Bioinformatics and Integrative Biology Universidad Andrés Bello Santiago 8370146 Chile.

Laboratorio Síntesis Orgánica, Instituto de Química de Recursos Naturales Universidad de Talca Casilla 747 Talca Chile.

出版信息

ChemistryOpen. 2019 May 21;8(5):627-636. doi: 10.1002/open.201900073. eCollection 2019 May.

DOI:10.1002/open.201900073
PMID:31139552
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6528641/
Abstract

The imino-Diels-Alder reaction is one of the most common strategies in organic chemistry and is an important tool for providing a broad spectrum of biologically active heterocyclic systems. A combined theoretical and experimental study of the imino-Diels-Alder reaction is described. The new phenanthroline-tetrahydroquinolines were evaluated as cholinesterase inhibitors. Their cytotoxicity in human neuroblastoma SH-SY5Y cells was also evaluated. The theoretical results suggest that compounds formation in stages can be explained by cycloadducts under the established reaction conditions, thereby confirming experimental results obtained for percentage yield. These results allowed us to establish that pyridine substituent remarkably influences activation energy and reaction yield, as well as in acetylcholinesterase (AChE) activity. Among these derivatives, compounds with 4-pyridyl and 4-nitrophenyl showed favorable AChE activity and proved to be non-cytotoxic.

摘要

亚氨基-狄尔斯-阿尔德反应是有机化学中最常见的策略之一，也是用于构建多种具有生物活性的杂环体系的重要工具。本文描述了对亚氨基-狄尔斯-阿尔德反应的一项理论与实验相结合的研究。新型菲咯啉-四氢喹啉被评估为胆碱酯酶抑制剂。还评估了它们在人神经母细胞瘤SH-SY5Y细胞中的细胞毒性。理论结果表明，在既定反应条件下，各阶段化合物的形成可用环加成物来解释，从而证实了所获得的产率百分比的实验结果。这些结果使我们能够确定吡啶取代基对活化能、反应产率以及乙酰胆碱酯酶（AChE）活性均有显著影响。在这些衍生物中，具有4-吡啶基和4-硝基苯基的化合物表现出良好的AChE活性，且被证明无细胞毒性。

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