Department of Inorganic Chemistry, Faculty of Sciences, University of Granada, Av. Fuentenueva S/N, Granada 18071, Spain.
Department of Physiology, University of Granada, Granada 18071, Spain.
Chem Commun (Camb). 2022 Feb 1;58(10):1514-1517. doi: 10.1039/d1cc04404d.
A new palladium coordination compound based on gliclazide with the chemical formula [Pd(glz)] (where glz = gliclazide) has been synthesized and characterised. The structural characterization reveals that this material consists of mononuclear units formed by a Pd ion coordinated to two molecules of the glz ligand, in which palladium ions exhibit a distorted plane-square coordination sphere. This novel material behaves like a good and selective inhibitor of butyrylcholinesterase, one of the most relevant therapeutic targets against Alzheimer's disease. Analysis of the enzyme kinetics showed a mixed mode of inhibition, the title compound being capable of interacting with both the free enzyme and the enzyme-substrate complex. Finally, the palladium compound shows promising protective activity against Aβ-induced toxicity in the model, which has never been reported.
一种新型基于格列齐特的钯配合物,化学式为[Pd(glz)](其中 glz = 格列齐特),已被合成并进行了表征。结构表征表明,该材料由单核单元组成,由钯离子与两个格列齐特配体分子配位而成,其中钯离子呈现出扭曲的平面正方形配位场。这种新型材料表现出良好的、对丁酰胆碱酯酶的选择性抑制作用,丁酰胆碱酯酶是对抗阿尔茨海默病的最相关治疗靶点之一。酶动力学分析表明,该化合物具有混合抑制模式,既能与游离酶相互作用,也能与酶-底物复合物相互作用。最后,该钯化合物在该模型中表现出对 Aβ诱导毒性的有前景的保护活性,这在以前从未报道过。