Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45137-66731, Iran.
Department of Chemistry, Institute for Advanced Studies in Basic Sciences (IASBS), Gava Zang, Zanjan 45137-66731, Iran.
Biophys Chem. 2018 Apr;235:56-65. doi: 10.1016/j.bpc.2018.02.005. Epub 2018 Feb 12.
Amyloid deposition, arising from the fibrillogenesis of proteins in organs and tissues of the body, causes several neurodegenerative disorders. One therapeutic approach is based on the use of polyphenols and their derivatives for suppressing and inhibiting the accumulation of these toxic fibrils in tissues. In the present study, the anti-amyloidogenic activities of bisdemethoxycurcumin (BDMC), a natural polyphenolic compound, and diacetylbisdemethoxycurcumin (DABC), a synthetic derivative of curcumin, on the amyloid fibrillation of hen egg white lysozyme (HEWL) is studied in depth using thioflavin T (ThT) fluorescence, atomic force microscopy (AFM), circular dichroism spectroscopy (CD), molecular docking and Ligplot calculations. The binding parameters such as binding constants and the number of substantive binding sites were obtained experimentally. It could be shown from docking simulation that four hydrogen bonds via the two phenolic OH groups of BDMC and two β-diketone moiety of BDMC are formed with the Asp-101, Trp-63, Asn-59 and Glu-35 of HEWL, whereas, two hydrogen bonds formed via two β-diketone moiety of DABC with Asn-39 and Trp-63 of HEWL. The short Fӧrster's distance (r) between donor and acceptor, the binding constant values and also the nature of interaction, demonstrate strong interaction between these two curcuminoids and lysozyme. According to amyloid fibrillation and binding results, the interaction of BDMC with HEWL is stronger than that of DABC and amyloid fibrillation of HEWL was inhibited more effectively by BDMC than DABC. It can be suggested that the more inhibitory activity of BDMC than DABC is correlated to the stronger interaction of BDMC with HEWL. These natural polyphenolic compounds are thus good candidates for inhibiting of amyloid formation. The inhibitory activities of BDMC and DABC can be used in drug formulation against the dangerous amyloid-related diseases and provide health promotion for organs and tissues of the body.
淀粉样蛋白沉积是由体内器官和组织中蛋白质的纤维形成引起的，它会导致几种神经退行性疾病。一种治疗方法是基于使用多酚及其衍生物来抑制和抑制这些有毒纤维在组织中的积累。在本研究中，深入研究了天然多酚化合物双去甲氧基姜黄素（BDMC）和姜黄素的合成衍生物二乙酰双去甲氧基姜黄素（DABC）对鸡卵清溶菌酶（HEWL）淀粉样蛋白纤维形成的抗淀粉样蛋白形成活性，使用硫黄素 T（ThT）荧光、原子力显微镜（AFM）、圆二色性光谱（CD）、分子对接和 Ligplot 计算。实验获得了结合常数和实质结合位点数等结合参数。对接模拟表明，BDMC 的两个酚羟基和 BDMC 的两个β-二酮部分通过与 HEWL 的 Asp-101、Trp-63、Asn-59 和 Glu-35 形成四个氢键，而 DABC 的两个β-二酮部分与 HEWL 的 Asn-39 和 Trp-63 形成两个氢键。供体和受体之间的短 Förster 距离（r）、结合常数值以及相互作用的性质表明，这两种姜黄素类化合物与溶菌酶之间存在强烈的相互作用。根据淀粉样蛋白纤维形成和结合结果，BDMC 与 HEWL 的相互作用强于 DABC，BDMC 对 HEWL 的淀粉样蛋白纤维形成的抑制作用强于 DABC。可以认为，BDMC 比 DABC 更强的抑制活性与 BDMC 与 HEWL 更强的相互作用有关。因此，这些天然多酚化合物是抑制淀粉样蛋白形成的良好候选物。BDMC 和 DABC 的抑制活性可用于针对危险的淀粉样相关疾病的药物配方，并为身体的器官和组织提供健康促进。
