Analytical Chemistry Research Group, Department of Chemical Sciences, University of Padova, via Marzolo 1, 35131 Padova, Italy.
Biomolecules. 2019 Jul 9;9(7):269. doi: 10.3390/biom9070269.
The present review reports a list of approximately 800 compounds which have been used, tested or proposed for Parkinson's disease (PD) therapy in the year range 2014-2019 (April): name(s), chemical structure and references are given. Among these compounds, approximately 250 have possible or established metal-chelating properties towards Cu(II), Cu(I), Fe(III), Fe(II), Mn(II), and Zn(II), which are considered to be involved in metal dyshomeostasis during PD. Speciation information regarding the complexes formed by these ions and the 250 compounds has been collected or, if not experimentally available, has been estimated from similar molecules. Stoichiometries and stability constants of the complexes have been reported; values of the cologarithm of the concentration of free metal ion at equilibrium (pM), and of the dissociation constant (both computed at pH = 7.4 and at total metal and ligand concentrations of 10 and 10 mol/L, respectively), charge and stoichiometry of the most abundant metal-ligand complexes existing at physiological conditions, have been obtained. A rigorous definition of the reported amounts is given, the possible usefulness of this data is described, and the need to characterize the metal-ligand speciation of PD drugs is underlined.
本综述报告了大约 800 种化合物的列表，这些化合物在 2014-2019 年（4 月）期间被用于、测试或提出用于治疗帕金森病（PD）：名称、化学结构和参考文献。在这些化合物中，大约有 250 种具有可能的或已建立的金属螯合特性，针对 Cu(II)、Cu(I)、Fe(III)、Fe(II)、Mn(II)和 Zn(II)，这些金属被认为与 PD 期间的金属失衡有关。已经收集了这些离子和 250 种化合物形成的配合物的形态信息；如果没有实验可获得，则根据类似的分子进行了估计。报告了配合物的化学计量和稳定常数；在 pH = 7.4 和总金属和配体浓度分别为 10 和 10 mol/L 的条件下，计算了自由金属离子浓度的对数（pM）和离解常数的值（均在 pH = 7.4 和总金属和配体浓度分别为 10 和 10 mol/L 的条件下计算），以及在生理条件下存在的最丰富的金属-配体配合物的电荷和化学计量。给出了报告量的严格定义，描述了这些数据的可能用途，并强调了需要表征 PD 药物的金属-配体形态。
