THEORETICAL STUDY OF POTENTIAL AGENTS FOR THE TREATMENT OF ALZHEIMER'S DISEASE 8-HIDROXYQUINOLINE DERIVATIVES WITH N-ACYLHIDRAZONE TYPE SUBSTITUENTS

In this work, Density Functional Theory was used in the theoretical study of the coordination of three ligands derived from 8-hydroxyquinoline (8-HQ) with N-acylhydrazone: 8-hydroxyquinoline-2-carboxaldehyde isonicotinoyl hydrazone (INHHQ), 2-[(8-hydroxyquinolinyl)methylene] acetohydrazide (8-H2QH) and 2-[(8-hydroxyquinolinyl)methylene] hydrazinecarboxamide (8-H2QS); with the Zn2+ion. These complexes prevent interactions of the metal ions present in the brain, with the β-amyloid peptide (Aβ), avoiding the formation of aggregates that are responsible for the development of the Alzheimer's disease. The results show that the three ligands coordinate the Zn2+ion in a tridentate form through the O and N atoms of the 8-hydroxyquinoline center and the N of the hydrazonic group, completing the coordination sphere with two chloride ions, creating a bipyramidal structure trigonal, different from the structures of the complexes reported in the literature.

本研究采用密度泛函理论（Density Functional Theory），对三类衍生自8-羟基喹啉（8-hydroxyquinoline，8-HQ）与N-酰基腙的配体与锌离子（Zn²+）的配位过程开展理论研究：这三类配体分别为8-羟基喹啉-2-甲醛异烟酰腙（INHHQ）、2-[(8-羟基喹啉基)亚甲基]乙酰肼（8-H2QH）以及2-[(8-羟基喹啉基)亚甲基]肼甲酰胺（8-H2QS）。此类配合物可阻断脑内金属离子与β-淀粉样肽（β-amyloid peptide，Aβ）的相互作用，进而避免诱导阿尔茨海默病发生的聚集体形成。研究结果显示，三类配体均通过8-羟基喹啉骨架的氧、氮原子以及腙基的氮原子以三齿形式与锌离子配位，并通过两个氯离子完成配位球结构，最终形成三角双锥构型，该构型与文献已报道的同类配合物结构存在差异。