Department of Chemistry, Indian Institute of Technology, Roorkee 247667, India.
Department of Chemistry, Indian Institute of Technology, Guwahati 781039, India.
Int J Biol Macromol. 2023 Sep 1;248:125847. doi: 10.1016/j.ijbiomac.2023.125847. Epub 2023 Jul 15.
Uncontrolled amyloid aggregation is a frequent cause of neurodegenerative disorders such as prions and Alzheimer's disease (AD). As a result, many drug development approaches focus on evaluating novel molecules that can alter self-recognition pathways. Herein, we designed and synthesized the cyclometallated pyrene (Pd-1 and Pd-3) and anthracene (Pd-2) based palladium complexes ([Pd((L)Cl] Pd-1, Pd(L)Cl, and [Pd(L)Cl] (Pd-3)). This study explores the effect of these complexes on the aggregation, fibrillation, and amyloid formation of bovine serum albumin (BSA) and Aβ peptide. Several spectroscopic methods were used to characterize all the Pd-complexes, and the molecular structure of Pd-3 was determined by X-ray crystallography. The secondary structures were studied using circular dichroism (CD) and transmission electron microscopy (TEM), while amyloid aggregation and inhibitory activities were investigated using the Thioflavin-T (ThT) fluorescence assay. Molecular docking of the Pd-complex (Pd-3) was done using fibril (PDB: 2BEG) and monomeric (PDB: 1IYT) peptides using Auto-dock Vina. As a result, the hydrogen bonding and hydrophobic interaction between the aromatic rings of the Pd-complexes and the amino acids of amyloid-β peptides significantly reduced the production of ordered β-sheets of amyloid fibrils and protein aggregation in the presence of Pd-2 and Pd-3 complexes.
无控制的淀粉样蛋白聚集是神经退行性疾病（如朊病毒和阿尔茨海默病）的常见原因。因此，许多药物开发方法都集中在评估可以改变自我识别途径的新型分子上。在这里，我们设计并合成了基于环金属化的芘（Pd-1 和 Pd-3）和蒽（Pd-2）的钯配合物（[Pd((L)Cl]Pd-1、Pd(L)Cl和Pd(L)Cl）。这项研究探讨了这些配合物对牛血清白蛋白（BSA）和 Aβ肽聚集、纤维化和淀粉样形成的影响。使用几种光谱方法对所有 Pd 配合物进行了表征，并通过 X 射线晶体学确定了 Pd-3 的分子结构。使用圆二色性（CD）和透射电子显微镜（TEM）研究了二级结构，使用 Thioflavin-T（ThT）荧光测定法研究了淀粉样蛋白聚集和抑制活性。使用 Auto-dock Vina 对 Pd 配合物（Pd-3）进行了分子对接，对接的肽为纤维状（PDB：2BEG）和单体（PDB：1IYT）。结果表明，Pd 配合物的芳香环与淀粉样β肽的氨基酸之间的氢键和疏水相互作用显著减少了 Pd-2 和 Pd-3 配合物存在时有序β-折叠的淀粉样纤维和蛋白质聚集的产生。
